Clinical implication of novel drug resistance-conferring mutations in resistant tuberculosis.

Evolving novel and/or unfamiliar mutations are revolutionizing the pathways of antibiotic resistance of clinical tuberculosis. The accumulation and interaction of these poorly characterized mutations augment the complexity of resistant pathogenic strains and raise public health concerns. This article reviews our current understanding of the genetic changes that characterize drug resistance in tuberculosis and highlights the imperative for further investigations focusing on the effects of an individual mutation and interacting mutations with detailed strain epidemiology, particularly as these pertain to technology-limited countries with high tuberculosis incidence rates. Concomitantly, there is a need for the development, testing, and uptake of new tools for studying the effects of these mutations in drug resistance and fitness cost of the pathogen. Such genetic data are critical for effective localized and global tuberculosis control interventions and for accurate epidemiological predictions.

Detection of Severe Acute Respiratory Syndrome-Like, Middle East Respiratory Syndrome-Like Bat Coronaviruses and Group H Rotavirus in Faeces of Korean Bats.

Bat species around the world have recently been recognized as major reservoirs of several zoonotic viruses, such as severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), Nipah virus and Hendra virus. In this study, consensus primer-based reverse transcriptase polymerase chain reactions (RT-PCRs) and high-throughput sequencing were performed to investigate viruses in bat faecal samples collected at 11 natural bat habitat sites from July to December 2015 in Korea. Diverse coronaviruses were first detected in Korean bat faeces, including alphacoronaviruses, SARS-CoV-like and MERS-CoV-like betacoronaviruses. In addition, we identified a novel bat rotavirus belonging to group H rotavirus which has only been described in human and pigs until now. Therefore, our results suggest the need for continuing surveillance and additional virological studies in domestic bat.

In vitro assessment of the gastrointestinal tolerance and immunomodulatory function of Bacillus methylotrophicus isolated from a traditional Korean fermented soybean food.

AIMS: This study aimed to investigate the potential of Bacillus methylotrophicus as a probiotic. METHODS AND RESULTS: A Bacillus isolate designated strain C14 was isolated from Korean traditional fermented soybean paste (doenjang). The strain was identified, and its physiological and biochemical properties were characterized. The gastrointestinal tolerance and immunomodulatory function of strain C14 were also investigated. Strain C14 was identified as B. methylotrophicus by analysis of its biochemical properties using the API 50CHB system and by phylogenetic analysis of the 16S rDNA sequence. Strain C14 showed >80% and >75% of survival for artificial gastric juices (pH 2.5 and 1% pepsin) and 0.5% (w/v) bile salt, respectively. Heat-killed B. methylotrophicus C14 inhibited the adhesion of various pathogens and enhanced the adhesion of probiotic bacteria to Caco-2 cells. The heat-killed cells also induced high levels of immune cell proliferation compared with the control and stimulated interleukin-6 and tumour necrosis factor-α production in mouse macrophages. CONCLUSIONS: Bacillus methylotrophicus C14 could be used as a probiotic. SIGNIFICANCE AND IMPACT OF THE STUDY: Recently identified B. methylotrophicus is a new potential probiotic with high gastrointestinal tolerance.

RIP2/RICK-dependent cytokine production upon Yersinia enterocolitica infection in macrophages with TLR4 deficiency.

Receptor-interacting protein 2 (RIP2) is a caspase recruitment domain (CARD)-containing serine/threonine kinase that is activated by NOD1 or NOD2 recognition of their ligands and essential for the activation of NF-κB and mitogen-activated protein kinase (MAPK). RIP2 has been known to play an important role in innate immune responses against certain bacterial infection. However, the role and interplay of RIP2 with TLR signalling on cytokine production in macrophages against Yersinia enterocolitica infection remains poorly understood. In the present study, we examined whether RIP2 is essential for Yersinia-induced production of cytokines in macrophages. Our results showed that naïve RIP2-deficient macrophages produced similar level of IL-6, TNF-α and IL-10 upon Y. enterocolitica infection compared with wild-type macrophages. However, the production of IL-6, TNF-α and IL-10 by Y. enterocolitica was impaired in RIP2-deficient macrophages after lipopolysaccharide (LPS) pretreatment, a TLR4-tolerant condition. In addition, RIP2 inhibitors, SB203580, PP2, and gefitinib, reduced IL-6 production in TLR4-deficient macrophages in response to Y. enterocolitica, whereas they did not affect the cytokines production in WT cells. These results demonstrate that RIP2 may play an important role in proinflammatory cytokine production in macrophages at the absence of TLR signalling.

p21-Activated kinase 4 promotes prostate cancer progression through CREB.

Prostate cancer is initially androgen-dependent but, over time, usually develops hormone- and chemo-resistance. The present study investigated a role for p21-activated kinase 4 (PAK4) in prostate cancer progression. PAK4 activation was markedly inhibited by H89, a specific protein kinase A (PKA) inhibitor, and PAK4 was activated by the elevation of cAMP. The catalytic subunit of PKA interacted with the regulatory domain of PAK4, and directly phosphorylated PAK4 at serine 474 (S474). Catalytically active PAK4 enhanced the transcriptional activity of CREB independent of S133 phosphorylation. Stable knockdown of PAK4 in PC-3 and DU145 prostate cancer cells inhibited tumor formation in nude mice. Decreased tumorigenicity correlated with decreased expression of CREB and its targets, including Bcl-2 and cyclin A1. Additionally, in androgen-dependent LNCap-FGC cells, PAK4 regulated cAMP-induced neuroendocrine differentiation, which is known to promote tumor progression. Finally, PAK4 enhanced survival and decreased apoptosis following chemotherapy. These results suggested that PAK4 regulates progression toward hormone- and chemo-resistance in prostate cancer, and this study identified both a novel activation mechanism and potential downstream effector pathways. Therefore, PAK4 may be a promising therapeutic target in prostate cancer.

Inferior paralabral ganglion cyst of the shoulder with labral tear -- a rare cause of shoulder pain.

INTRODUCTION: Paralabral ganglion cysts of the shoulder are rare, and their pathogenesis is similar to that of meniscal cysts. The paralabral cysts are most frequently reported along the posterior, superior, and anterior aspects of the glenohumeral joint and are uncommon inferiorly to the joint. These cysts rarely become evident clinically, unless they cause compression of surrounding structures, i.e. nerve. PATIENTS AND METHODS: We report a retrospective series of five patients with inferior paralabral ganglion cysts of the shoulder without compression of the surrounding nerve which were treated during the period from March 2007 to December 2009. All these patients presented with only chronic shoulder pain as their chief complaint, and preoperative MRI showed the cyst over the inferior aspect of a torn glenoid labrum. All patients were treated by arthroscopic cystic decompression with labrum repair. All patients were re-evaluated with MRI performed at an average of 15 months postoperatively. The clinical outcome, including the Constant score, was assessed for all patients at a median of 16 months postoperatively. RESULTS: All the five patients had remission of pain and were satisfied with the shoulder function. The postoperative MRI in all patients showed no labral cyst recurrence. The median Constant score improved from a preoperative level of 81.5 points to 98.0 points at last follow-up. CONCLUSION: This study demonstrates that, in the absence of any nerve compression symptoms around the shoulder joint, inferior paralabral cysts with labral tear also be considered in the differential diagnosis of chronic shoulder pain. Arthroscopic repair of the cyst with repair of the labrum can lead to the disappearance of symptoms. Knowledge of this clinical condition and its imaging features is critical for a correct diagnosis of this uncommon cause of chronic shoulder pain. LEVEL OF EVIDENCE: Level IV. Retrospective therapeutic study.

Cerebral arterial compliance in patients with internal carotid artery disease.

BACKGROUND: A decrease in arterial compliance of the internal carotid artery has been associated with an increased risk in ipsilateral ischaemic stroke. However, so far, no technique has been validated to monitor the compliance of intracerebral arteries (Ca) in patients with carotid artery disease. In this study, we sought to monitor Ca in patients with unilateral symptomatic disease and to determine its variations during changes in PaCO(2). METHODS: We studied 18 patients with unilateral symptomatic internal carotid artery stenosis >50% or occlusion. Patients underwent monitoring of arterial blood pressure (ABP) and middle cerebral artery cerebral blood flow velocities (CBFV) during baseline, hyperventilation and 5%CO(2) inhalation. Ca was calculated from pulsatile amplitudes of ABP and Cerebral arterial blood volume, extracted from the CBFV waveform using a new mathematical model. RESULTS: At baseline, the decrease in Ca on the diseased side was correlated with the degree of stenosis (r = -0.35; P = 0.01). During hypocapnia, Ca was lower compared to baseline on the normal side (P = 0.004) and on the diseased side (P = 0.04). Ca reactivity, reflecting the changes in Ca per changes in 1 mmHg PaCO(2), was lower on the diseased side between baseline and hypocapnia (3.4 vs. 2.6%; P = 0.04). During hypercapnia, no changes in Ca on the diseased (P = 0.8) nor on the normal sides (P = 0.2) were observed. CONCLUSIONS: The decrease in cerebral arterial compliance the side of stenosis/occlusion was correlated with the severity of the internal carotid artery disease. Further studies are needed to determine whether Ca may improve the prediction of ischaemic events in symptomatic and asymptomatic patients.

Spontaneous basal cell carcinoma in a 7-week-old Sprague-Dawley rat.

Spontaneous basal cell carcinoma (BCC) is very rare in rats, with an incidence rate of only 0.14% reported in aged animals. A spontaneous BCC occurred in a 7-week-old Sprague-Dawley rat housed in a specific-pathogen-free animal facility. The tumor was a single, well-delineated reddish-brown subcutaneous mass measuring 2 x 2 cm and located in the left inguinal region. Microscopically, the tumor consisted of basaloid cells in lobular and cribriform growth patterns and with a high mitotic rate. Immunohistochemically, cytokeratin 14 (an indicator for basal keratinocytes of the epidermis) showed strong reactions throughout the whole tumor, and cytokeratin 18 showed weak but positive reaction in the majority of nested tumor cells. To the authors' knowledge, this is the first report of spontaneous BCC occurrence in young Sprague-Dawley rats.

Modeling of growth kinetics for Pseudomonas putida during toluene degradation.

Glucose has been often used as a secondary substrate to enhance the degradation of primary substrate as well as the increase of biomass, especially for the inhibitory range of substrate concentration. In this study, we investigated the effect of glucose concentration on growth kinetics of Pseudomonas putida during toluene degradation for a wide concentration range (60-250 mg/l). Batch microcosm studies were conducted in order to monitor bacterial growth for three different initial concentrations (2, 5, 10 mg/ml) of glucose for a given toluene concentration. Modeling of growth kinetics was also performed for each growth curve of glucose dose using both Monod and Haldane kinetics. Batch studies revealed that bacterial growth showed a distinct inhibitory phase above some limit (approximately 170 mg/l) for the lowest (2 mg/ml) glucose dose, but the degree of inhibition decreased as the glucose dose increased, leading to three different growth patterns. The bacterial growth followed each of the modified Wayman and Tseng, Wayman and Tseng, and Luong model as the glucose dose increased from 2 to 10 mg/ml. This indicates that glucose has a prominent influence on bacterial growth during toluene degradation and that different kinetics should be adopted for each broth condition.

Embolisation of indirect carotid-cavernous sinus dural arterio-venous fistulae using the direct superior ophthalmic vein approach.

Indirect carotid-cavernous sinus dural arterio-venous fistulae (cDAVF) can be treated by transarterial and/or transvenous embolisation. This study evaluated patients with cDAVF who underwent transvenous embolisation using the direct superior ophthalmic vein (SOV) approach. Between January 2004 and October 2006, eight cDAVF in seven patients were embolised using direct surgical exposure of the SOV when access to the cDAVF via transarterial or transfemoral venous routes was not feasible. Medical records and imaging studies were retrospectively reviewed. The seven patients consisted of four females and three males from 43 to 65-year-old (mean age, 54.4 years). Six cDAVF lesions were located on the left side and two on the right. All fistulae were successfully embolised and showed clinical improvement. One patient presented after treatment with transient venous congestion on the brain stem, which was relieved by osmotic diuretics and steroids. Direct surgical exposure of the SOV for transvenous embolisation of cDAVF can be effective if the facial vein, inferior petrosal sinus, and internal jugular vein are thrombosed. This approach is easy, safe, and effective when performed by a multidisciplinary team.

Effect of regular exercise on senile dementia patients.

Dementia population worldwide is considerable in elderly people. Exercise regulates the brain function, but the mechanism by which it does so is unknown. The effect of regular exercise on cognitive function and exercise capacity in senile dementia patients was investigated. Thirty female patients with senile dementia who participated in the study were divided into two groups: the exercise group (EG, n = 15) and the control group (CG, n = 15). The exercise group completed a regular exercise program, and their cognitive function, activities of daily living and exercise capacity levels were evaluated at baseline, 6 months and after 12 months. Subjects exercised 30 - 60 minutes per day, 2 - 3 times per week for 12 months. Mini-mental state examination (MMSE) (pre: 14.53 +/- 5.34, post: 17.47 +/- 6.90) and ADL (pre: 14.40 +/- 5.32, post: 17.53 +/- 5.46) scores were significantly enhanced in the exercise group with senile dementia, compared to those in the control group. Exercise capacities such as cardiopulmonary function (pre: 128.47 +/- 55.43, post: 184.40 +/- 41.16), muscle strength (pre: 10.07 +/- 3.61, post: 13.7 +/- 3.90), muscular endurance (pre: 8.13 +/- 4.45, post: 12.13 +/- 5.14), flexibility (- 1.53 +/- .30, post: 2.20 +/- .70, balance (pre: 1.73 +/- .28, post: 1.20 +/- .77), and agility (pre: 21.80 +/- 3.24, post: 10.87 +/- 2.99) also increased in the exercise group. Our findings showed that regular exercise can enhance cognitive and functional activity scores in dementia patients, suggesting that senile dementia may improve by participating in a regular exercise program.

Desorption kinetics of benzene in a sandy soil in the presence of powdered activated carbon.

Desorption kinetics of benzene was investigated with a modified biphasic desorption model in a sandy soil with five different powdered activated carbon (PAC) contents (0, 1, 2, 5, 10% w/w) as sorbents. Sorption experiments followed by series dilution desorption were conducted for each sorbent. Desorption of benzene was successively performed at two stages using deionized water and hexane. Modeling was performed on both desorption isotherm and desorption rate for water-induced desorption to elucidate the presence of sorption-desorption hysteresis and biphasic desorption and if present to quantify the desorption-resistant fraction (q (irr)) and labile fraction (F) of desorption site responsible for rapid process. Desorption isotherms revealed that sorption-desorption exhibited a severe hysteresis with a significant fraction of benzene being irreversibly adsorbed onto both pure sand and PAC, and that desorption-resistant fraction (q (irr)) increased with PAC content. Desorption kinetic modeling showed that desorption of benzene was biphasic with much higher (4-40 times) rate constant for rapid process (k (1)) than that for slow process (k (2)), and that the difference in the rate constant increased with PAC content. The labile fraction (F) of desorption site showed a decreasing tendency with PAC. The experimental results would provide valuable information on remediation methods for soils and groundwater contaminated with BTEX.

Attenuation of aqueous benzene in soils under saturated flow conditions.

The fate of aqueous benzene in subsurface was investigated in this study, focusing on the role of sorption and biodegradation on the benzene attenuation under dynamic flow conditions. Two sets of column tests were conducted in Plexiglass flow cells packed uniformly with sandy aquifer materials. The first set of the experiment was conducted with a step-type injection of benzene with different powder activated carbon (PAC) contents: (1) PAC = 0 %; (2) PAC = 0.5 %; (3) PAC = 2.0%. The second set was performed as a pulse-type with different test conditions: (4) benzene; (5) benzene and bacteria (Pseudomonas aeruginosa); (6) benzene and bacteria (P. aeruginosa) with hydrogen peroxide. In addition, numerical experiments were performed to examine the role of sorption processes on the benzene attenuation. In the step mode experiments, the KCl breakthrough curves (BTCs) reached the input concentration while the benzene BTCs were considerably lower than those of KCl with slight retardation for all cases, indicating that both reversible/retardation and irreversible sorption occurred. The pulse type tests showed that attenuation of benzene increased in the presence of bacteria due to biodegradation. The benzene attenuation by microbial degradation increased furthermore in the presence of hydrogen peroxide owing to sufficient supply of dissolved oxygen in soil column. Numerical experiments demonstrated that retardation could not contribute to the attenuation of benzene in soils but could only extend its breakthrough time. Experimental results indicated that aqueous benzene could be attenuated by irreversible sorption and biodegradation during transport through the subsurface. Additionally, the attenuation of aqueous benzene is closely related to organic carbon content and oxygen level existing in contaminated aquifers.

Purification and characterization of tannase from Paecilomyces variotii: hydrolysis of tannic acid using immobilized tannase.

An extracellular tannase (tannin acyl hydrolase) was isolated from Paecilomyces variotii and purified from cell-free culture filtrate using ammonium sulfate precipitation followed by ion exchange and gel filtration chromatography. Fractional precipitation of the culture filtrate with ammonium sulfate yielded 78.7% with 13.6-folds purification, and diethylaminoethyl-cellulose column chromatography and gel filtration showed 19.4-folds and 30.5-folds purifications, respectively. Molecular mass of tannase was found 149.8 kDa through native polyacrylamide gel electrophoresis (PAGE) analysis. Sodium dodecyl sulphate-PAGE revealed that the purified tannase was a monomeric enzyme with a molecular mass of 45 kDa. Temperature of 30 to 50 degrees C and pH of 5.0 to 7.0 were optimum for tannase activity and stability. Tannase immobilized on alginate beads could hydrolyze tannic acid even after extensive reuse and retained about 85% of the initial activity. Thin layer chromatography, high performance liquid chromatography, and (1)H-nuclear magnetic resonance spectral analysis confirmed that gallic acid was formed as a byproduct during hydrolysis of tannic acid.

Differences in radiological/HRCT findings in eosinophilic bronchitis and asthma: implication for bronchial responsiveness.

BACKGROUND: Airway hyperresponsiveness in asthmatics is considered to be one of the major consequences of airway inflammation and remodelling. Airway responsiveness is normal in patients with eosinophilic bronchitis (EB), despite eosinophilic inflammation of the airways comparable to that which occurs in asthmatics. Comparisons between asthma and EB should clarify the changes in airway morphology that are related specifically to AHR in asthmatics. METHODS: Eighteen asthmatic patients, 15 patients with EB, and 11 healthy subjects were recruited. Airway wall area percentage (WA%), centrilobular prominence, and air trapping were compared using thin slice section computed tomography. RESULTS: WA% was significantly greater in asthmatics than in patients with EB (72 (3.1)% v 54 (2.1)%, p = 0.032) and was similar in EB patients and controls (54 (2.1)% v 57 (1.8)%, p>0.05). Centrilobular prominence and air trapping were similar in EB patients and asthmatics and were significantly greater than in controls. CONCLUSION: WA% rather than air trapping or centrilobular prominence may be associated with the airway hyperresponsiveness that occurs in asthmatics but not in patients with EB.

Effect of dissolved oxygen regime on growth dynamics of Pseudomonas spp during benzene degradation.

We investigated the effect of different oxygen regimes on growth patterns of Pseudomonas spp. during benzene degradation in microcosm batch studies. Benzene degradation was induced by limiting oxygen available for microbial activity, which consists of three initial-dissolved oxygen (DO) levels of oxic, hypoxic, and anoxic conditions. Batch experiments were performed for cell growth and benzene degradation by inoculating three strains of Pseudomonas spp. (Pseudomonas aeruginosa, Pseudomonas fluorescens, Pseudomonas putida) in mineral salt medium containing aqueous benzene. Results showed that all strains were capable to grow and degrade benzene under all oxygen regimes but in a different manner. The highest cell growth of P. aeruginosa and P. fluorescens was achieved under oxic and anoxic condition, respectively, but there was no substantial difference on benzene degradation between the oxygen treatments with about 25% reduction for both strains. P. putida showed a facultative process for both cell growth and benzene degradation. This reveals that care should be taken in selection of microorganisms with regard to environmental studies since they exhibit different responses for given environmental conditions such as DO levels.

Serum gamma-glutamyltransferase within its normal concentration range is related to the presence of diabetes and cardiovascular risk factors.

AIMS: Although many studies have reported an association between serum gamma-glutamyltransferase (GGT) and cardiovascular risk factors, the mechanism of this relationship has not been clarified. METHODS: The medical records of 29,959 subjects (age, median 48, range 14-90 years; 16,706 men, 13,253 women) who visited the Center for Health Promotion at Samsung Medical Center for a medical check-up between January 2001 and December 2003, were investigated. Subjects with hepatic enzyme/GGT concentrations higher than three times the upper limit of the reference range, a positive test for hepatitis C virus antibody, a positive test for hepatitis B virus surface antigen, currently taking anti-diabetic/anti-hypertensive/anti-lipid medication, or a white blood cell (WBC) count higher than 10,000 cells/ml, were excluded. The subjects of each gender were classified into five groups according to their serum GGT concentrations, into quartiles of the normal range of GGT (groups 1, 2, 3 and 4) and into a group with elevated GGT (group 5). RESULTS: As the group number increased (group 1 --> 5), the frequencies of all of the following increased: (i) diabetes and impaired fasting glucose (IFG); (ii) hypertension, obesity (body mass index > or = 27 kg/m2), dyslipidaemia (LDL-cholesterol > or = 4.1 mmol/l and/or triglyceride > or = 2.46 mmol/l, or HDL-cholesterol < 1.16 mmol/l); (iii) metabolic syndrome. Moreover, these significant relationships between GGT concentrations within its normal range and the presence of diabetes/IFG, hypertension, obesity, dyslipidaemia, and metabolic syndrome persisted after adjusting for several clinical and biochemical variables and for the presence of fatty liver based on ultrasonographic findings. Odds ratios (95% CI) for group 4 (highest quartile of normal range of GGT) vs. group 1 (lowest quartile of normal range of GGT); the referent group, were 3.16 (2.15-4.65) for diabetes, 2.24 (1.73-2.90) for IFG, 1.93 (1.59-2.33) for obesity, 1.38 (1.23-1.55) for dyslipidaemia and 2.88 (2.28-3.65) for metabolic syndrome in men. In women, the odds ratios were 2.72 (1.34-5.52), 3.67 (2.26-5.97), 2.10 (1.61-2.74), 1.80 (1.58-2.04) and 3.57 (2.52-5.07), respectively. CONCLUSIONS: Our data show that, even within its normal range, serum GGT concentrations are closely associated with the presence of diabetes and cardiovascular risk factors, and that these associations are independent of a fatty liver by ultrasonography.

Modeling of growth kinetics for Pseudomonas spp. during benzene degradation.

A modeling study was conducted on growth kinetics of three different strains of Pseudomonas spp. (Pseudomonas aeruginosa, Pseudomonas fluorescens, Pseudomonas putida) during benzene degradation to determine optimum substrate concentrations for most efficient biodegradation. Batch tests were performed for eight different initial substrate concentrations to observe cell growth and associated substrate degradation using benzene-adapted cells. Kinetic parameters of both inhibitory (Haldane-Andrews, Aiba-Edwards) and noninhibitory (Monod) models were fitted to the relationship between specific growth rate and substrate concentration obtained from the growth curves. Results showed that half-saturation constant of P. fluorescens was the highest among the three strains, indicating that this strain could grow well at high concentration, while P. putida could grow best at low concentration. The inhibition constant of P. aeruginosa was the highest, implying that it could tolerate high benzene concentration and therefore could grow at a wider concentration range. Estimated specific growth rate of P. putida was lower, but half-saturation constant was higher than those from literature study due to high substrate concentration range used in this study. These two kinetic parameters resulted in substantial difference between Monod- and Haldane-type models, indicating that distinction should be made in applying those models.

Identification of new dinucleotide-repeat polymorphisms in factor VIII gene using fluorescent PCR.

Haemophilia A is an X-linked inherited bleeding disorder. Linkage diagnosis using polymorphic markers in the factor VIII gene is used to archive the carrier detection and prenatal diagnosis. The objective of this study was to establish the allele frequency and heterozygosity rate (HR) of two new intragenic markers (Intron 1 and 24) and other markers (Intron 13 and 22) using fluorescent PCR. Five hundred unrelated healthy women were screened and haemophilic family was studied for carrier detection and prenatal diagnosis. We observed five different alleles of Intron 1, 10 of Intron 24, nine of Intron 13 and six of Intron 22. The observed HR for Intron 1, 24, 13 and 22 were 34.0, 35.2, 53.0 and 42.6%, while the expected HR were 33.6, 36.3, 50.1 and 44.3%, respectively. Heterozygosity rate with the combined use of all four intragenic markers was 76.6% (383/500). In prenatal diagnosis of a haemophilic family, a pregnant woman was heterozygous with three intragenic (Intron 1, 13 and 22) and one extragenic St14 VNTR (DXS52) markers. She was considered to be a carrier, and she carried a male foetus by AMXY PCR and chromosome analysis of amniocytes. Foetus did not have mutant haplotype as his uncle, suggesting a normal male status. Our study demonstrates the utility of two new intragenic markers in FVIII gene for carrier detection and prenatal diagnosis of haemophilic families.

Natural killer cell activity and quality of life were improved by consumption of a mushroom extract, Agaricus blazei Murill Kyowa, in gynecological cancer patients undergoing chemotherapy.

A mushroom extract, Agaricus blazei Murill Kyowa (ABMK), has been reported to possess antimutagenic and antitumor effects. Here, we investigate the beneficial effects of ABMK consumption on immunological status and qualities of life in cancer patients undergoing chemotherapy. One hundred cervical, ovarian, and endometrial cancer patients were treated either with carboplatin (300 mg / m(2)) plus VP16 (etoposide, 100 mg / m(2)) or with carboplatin (300 mg / m(2)) plus taxol (175 mg / m(2)) every 3 weeks for at least three cycles with or without oral consumption of ABMK. We observed that natural killer cell activity was significantly higher in ABMK-treated group (ANOVA, n = 39, P < 0.002) as compared with nontreated placebo group (n = 61). However, no significant difference in lymphokine-activated killer and monocyte activities was observed in a manner similar to the count of specific immune cell populations between ABMK-treated and nontreated groups. However, chemotherapy-associated side effects such as appetite, alopecia, emotional stability, and general weakness were all improved by ABMK treatment. Taken together, this suggests that ABMK treatment might be beneficial for gynecological cancer patients undergoing chemotherapy.