The microbiome of a Pacific moon jellyfish Aurelia coerulea.

The impact of microbiome in animal physiology is well appreciated, but characterization of animal-microbe symbiosis in marine environments remains a growing need. This study characterizes the microbial communities associated with the moon jellyfish Aurelia coerulea, first isolated from the East Pacific Ocean and has since been utilized as an experimental system. We find that the microbiome of this Pacific Aurelia culture is dominated by two taxa, a Mollicutes and Rickettsiales. The microbiome is stable across life stages, although composition varies. Mining the host sequencing data, we assembled the bacterial metagenome-assembled genomes (MAGs). The bacterial MAGs are highly reduced, and predict a high metabolic dependence on the host. Analysis using multiple metrics suggest that both bacteria are likely new species. We therefore propose the names Ca. Mariplasma lunae (Mollicutes) and Ca. Marinirickettsia aquamalans (Rickettsiales). Finally, comparison with studies of Aurelia from other geographical populations suggests the association with Ca. Mariplasma lunae occurs in Aurelia from multiple geographical locations. The low-diversity microbiome of Aurelia provides a relatively simple system to study host-microbe interactions.

Population pharmacokinetics of phenobarbital by mixed effect modelling using routine clinical pharmacokinetic data in Japanese neonates and infants: an update.

WHAT IS KNOWN AND OBJECTIVE: Optimal use of phenobarbital in the neonatal population requires information regarding the drug's pharmacokinetics and the influence of various factors, such as different routes of administration, on the drug's disposition. However, because of sampling restrictions, it is often difficult to perform traditional pharmacokinetic studies in neonates and infants. This study was conducted to establish the role of patient characteristics in estimating doses of phenobarbital for neonates and infants using routine therapeutic drug monitoring data. METHODS: The population pharmacokinetics of phenobarbital was evaluated using 109 serum concentration measurements obtained from routine phenobarbital monitoring of 70 neonates and infants. The data were analysed using the non-linear mixed effects model. A one-compartment pharmacokinetic model with first-order elimination was used. Covariates screened were current total bodyweight (TBW), gestational age, postnatal age (PNA), post-conceptional age, gender and neonates-infants clearance factor (serum concentration of phenobarbital; Conc). RESULTS AND DISCUSSION: The final pharmacokinetic parameters were CL/F (mL/h) = (5.95.TBW (kg) +1.41.PNA (weeks)) Conc (serum phenobarbital concentration >50 µg/mL)(-0.221),Vd/F(L) =1.01.TBW (kg), and F = 0.483 for oral administration and F = 1 was assumed for suppository. Conc(-0.221) is 1 for phenobarbital concentration <50 µg/mL. The important variables for predicting phenobarbital clearance in this study were TBW, PNA and Conc. Phenobarbital clearance increases proportionately with increasing TBW, and an older newborn was expected to have a higher rate of clearance than a younger newborn of equal bodyweight. Moreover, the clearance of phenobarbital decreased nonlinearly with increasing serum concentration of phenobarbital >50 µg/mL (Conc(-0.221) ). WHAT IS NEW AND CONCLUSION: We developed a new model for neonate and infant dosing of phenobarbital with good predictive performance. Clinical application of our model should permit more accurate selection of initial and maintenance doses to achieve target phenobarbital concentrations in Japanese neonates and infants, thereby enabling the clinician to achieve the desired therapeutic effect. A similar approach can be used to validate our model for use in other neonate and infant populations.

The relationship between histomorphological characteristics and Ki-67 proliferation index in meningiomas.

OBJECTIVES: This study had two aims. The first was to use the Ki 67 proliferation index (Ki-67 PI) to study the relationship between the proliferation potential and histopathological features such as mitosis, necrosis, loss of architecture, small cell change, hypercellularity, pleomorphism, brain invasion, dura invasion, bone invasion, and histological grade. The second aim was to compare primary and recurrent meningioma with respect to morphological characteristics and Ki-67 PI values. BACKGROUND: Meningiomas are tumors whose histological features do not predict their biological behavior. Despite their slow growth and even after total resection, recurrence may occur METHODS: A total of 245 meningioma cases in whom Ki-67 PI was studied were included in the study. The cases were assessed with respect to 10 morphological characteristics, and a possible significant relationship between these and Ki 67 PI was statistically tested. RESULTS: We found a statistically significant relationship between Ki-67 PI and mitotic activity, necrosis, loss of architecture, small cell change, brain invasion. In contrast to brain invasion, no significant relationship was present between dura or bone invasion and Ki-67 PI. We identified asignificant increase in the histological grade, mitotic activity and Ki-67 PI value of recurrent tumors, as compared to primary ones CONCLUSION: Ki-67 PI values overlap in different grades. This overlapping might be due to the heterogeneity of biological activity within the tumor tissue (Tab. 2, Fig. 7, Ref. 21).

Purging deleterious mutations under self fertilization: paradoxical recovery in fitness with increasing mutation rate in Caenorhabditis elegans.

BACKGROUND: The accumulation of deleterious mutations can drastically reduce population mean fitness. Self-fertilization is thought to be an effective means of purging deleterious mutations. However, widespread linkage disequilibrium generated and maintained by self-fertilization is predicted to reduce the efficacy of purging when mutations are present at multiple loci. METHODOLOGY/PRINCIPAL FINDINGS: We tested the ability of self-fertilizing populations to purge deleterious mutations at multiple loci by exposing obligately self-fertilizing populations of Caenorhabditis elegans to a range of elevated mutation rates and found that mutations accumulated, as evidenced by a reduction in mean fitness, in each population. Therefore, purging in obligate selfing populations is overwhelmed by an increase in mutation rate. Surprisingly, we also found that obligate and predominantly self-fertilizing populations exposed to very high mutation rates exhibited consistently greater fitness than those subject to lesser increases in mutation rate, which contradicts the assumption that increases in mutation rate are negatively correlated with fitness. The high levels of genetic linkage inherent in self-fertilization could drive this fitness increase. CONCLUSIONS: Compensatory mutations can be more frequent under high mutation rates and may alleviate a portion of the fitness lost due to the accumulation of deleterious mutations through epistatic interactions with deleterious mutations. The prolonged maintenance of tightly linked compensatory and deleterious mutations facilitated by self-fertilization may be responsible for the fitness increase as linkage disequilibrium between the compensatory and deleterious mutations preserves their epistatic interaction.

Spontaneous remission of acute lymphoblastic leukemia with mediastinal mass.

Spontaneous remission/regression of cancer is defined as partial or complete disappearance of malignant disease temporarily or permanently in the absence of medical treatment. This event is named as spontaneous regression for solid tumors and spontaneous remission for leukemia. The authors report the case of a girl aged 4 years and 3 months, who presented with mediastinal mass and leukemic findings in the bone marrow both of which reappeared after spontaneous regression and remission, respectively.

Interaction between catechol-O-methyltransferase (COMT) Val108/158Met and brain-derived neurotrophic factor (BDNF) Val66Met polymorphisms in age at onset and clinical symptoms in schizophrenia.

Catechol-O-methyltransferase (COMT) gene is one of the candidate genes for schizophrenia because it codes an enzyme that participates in the metabolic inactivation of dopamine and noradrenaline and a limiting factor of dopamine metabolism in the prefrontal cortex. COMT gene lies on chromosome 22q11.2, which has been associated with schizophrenia susceptibility. A single-nucleotide polymorphism of COMT gene at position 108/158 results in an amino acid substitution from valine (val) to methionine (met), which modifies its enzymatic activity and may change the brain morphology and expressional behaviors. On the other hand, brain-derived neurotrophic factor (BDNF) plays a critical role in the development of mesolimbic dopaminergic- related systems. BDNF also contains a functional single-nucleotide polymorphism at codon 66 (Val66Met) of its prodomain and this polymorphism is responsible for schizophrenia susceptibility. In this study, we first investigated the relationship between COMT Val108/158Met polymorphism and age at onset as well as levels of clinical symptoms in 158 of chronic schizophrenia inpatients and then we investigated the gene-by-gene interaction between COMT Val108/158Met polymorphism and BDNF Val66Met polymorphism with age- and sex-matched control subjects (n = 318). We concluded that the COMT Val108/158Met polymorphism was not related to either the onset at age or the levels of clinical symptoms after long-term antipsychotic treatment in schizophrenia.

Miliary tuberculosis: clinical manifestations, diagnosis and outcome in 38 adults.

OBJECTIVE: The aim of the study was to determine the clinical, radiographic and laboratory characteristics, diagnostic methods, and prognostic variables in patients with miliary tuberculosis (TB). METHODOLOGY: The records of 38 patients (15 male, 23 female; mean age 41 years, range 16-76 years) with miliary TB from 1978 to 1998 were analyzed. Patients were evaluated also as to whether they presented with a fever of unknown origin (FUO). Criteria for the diagnosis of miliary TB were (i) miliary pattern on chest X-ray or (ii) biopsy or autopsy evidence of miliary organ involvement. Paraffin-embedded tissues with granulomata (n = 15) were re-evaluated for the presence of Mycobacterium tuberculosis DNA by polymerase chain reaction (PCR). RESULTS: Predisposing conditions were present in 24% of the patients. The findings were fever, weakness, night sweats, anorexia/weight loss (100% for each), hepatomegaly (37%), splenomegaly (32%), choroidal tubercles (13%), neck stiffness (11%), altered mental status (8%), anaemia (76%), leukopenia (26%), thrombocytopenia (16%), lymphopenia (76%), pancytopenia (8%) and hypertransaminasemia (55%). Eighteen patients (47%) met the criteria for a FUO. Miliary infiltrates were found on chest X-rays of 32 of 38 cases (84%). In six cases without miliary infiltrates, the diagnosis was made by laparotomy in four cases, and autopsy in two cases. Tuberculin skin test was positive in 32% of cases. Acid-fast bacilli were demonstrated in 37% (16/43), and cultures for M. tuberculosis were positive in 90% (9/10) of tested specimens (predominantly sputum and bronchial lavage). Granulomas were found in 85% (11/13) of lung, 100% (15/15) of liver, and 56% (9/16) of bone marrow tissue specimens. Acid-fast bacilli staining was negative in all (0/21), while PCR was positive in 47% (7/15) of specimens with granulomata. Mortality was 18%. Stepwise logistic regression identified male sex (P = 0.005), non-typical miliary pattern (P = 0.015), altered mental status (P = 0.002) and failure to treat for TB (P = 0.00001) as independent predictors of mortality. CONCLUSIONS: Miliary infiltrates on chest X-ray or FUO should raise the possibility of miliary TB. Therapy should be administered urgently to prevent an otherwise fatal outcome.

Multimodal inclusion complexes between barbiturates and 2-hydroxypropyl-beta-cyclodextrin in aqueous solution: isothermal titration microcalorimetry, (13)C NMR spectrometry, and molecular dynamics simulation.

Multiple types (structures) of inclusion complexes between barbiturates and 2-hydroxypropyl-beta-cyclodextrin (HPCD) were evaluated by isothermal titration microcalorimetry and (13)C NMR spectroscopy. The geometries of the inclusion complexes were suggested by molecular dynamics simulation. Barbituric acid (BA), barbital (B), amobarbital (AB), pentobarbital (PB), secobarbital (SB), cyclobarbital (CB), and phenobarbital (PHB) were used as barbiturates with different substituents on the barbituric acid ring and compared for inclusion types in aqueous solution. The association constants (K), stoichiometries, and thermodynamic parameters change in free energy (DeltaG) change in enthalpy (DeltaH), and change in entropy [DeltaS] for each type of complex were determined from the calorimetric data. The inclusion complexation was largely entropy driven because of hydrophobic interactions. The values of K increased in the order BA

Influence of pentoxifylline and interferon-alpha on prevention of stricture due to corrosive esophagitis. An experimental study in the rat.

The effects of pentoxifylline (PTX) and interferon alpha (IFN-alpha) in the prevention of strictures due to corrosive esophagitis in rats were investigated. Forty rats were randomly divided into four equal groups. Corrosive esophagitis was induced in all groups by application of 37.5% NaOH to the distal esophagus for a period of 90 s followed by saline rinse. Histopathologic damage was significantly lower in the PTX and IFN-alpha-treated groups than in the untreated group. During the study period, PTX and INF-alpha-treated animals showed a significant increase in body weight when compared to controls. However, PTX provided more significant prevention of stricture formation than IFN-alpha. In the PTX-treated group, the wall thickness and quantity of hydroxyprolin were significantly lower than in the untreated and IFN-alpha-treated groups. Stenosis index in the PTX group was significantly reduced compared to the control group. PTX prevents the stricture formation due to corrosive esophagitis in this experimental model. IFN-alpha was also shown to prevent stricture formation when considering amelioration of histopathologic damage and increase in body weight.

Anti-inflammatory effects of 5-aminosalicylic acid conjugates with chenodeoxycholic acid and ursodeoxycholic acid on carrageenan-induced colitis in guinea-pigs.

Two epimeric bile acid conjugates, 5-aminosalicylic acid-chenodeoxycholic acid (5-ASA-CDCA) and 5-aminosalicylic acid-ursodeoxycholic acid (5-ASA-UDCA), were synthesized to deliver 5-ASA to the large intestine by oral administration. The movement of the conjugates down the gastrointestinal tract and the anti-inflammatory effects on ulcerative colitis were investigated by administering the conjugates to guinea-pigs with an inflammatory bowel disease induced by 2% degraded carrageenan solution. The conjugates were protected from deconjugation in stomach and small intestine and reached the caecum and the colon, where 5-ASA was more easily liberated from 5-ASA-CDCA than from 5-ASA-UDCA. The conjugates at doses equivalent to 50 or 150 mg kg(-1) 5-ASA were orally administered once a day for 4 weeks from the 15th day after starting carrageenan treatment. The body weights and the bleeding scores of occult blood in faeces were measured during the experiment. The number of ulcers in the caecum and the colon were counted after killing the guinea-pigs at the end of the experiment. Rapid onset of efficacy was shown by a significant reduction in bleeding scores within a week after administration of the conjugates. Treatment with the lower dose of 5-ASA-CDCA showed a recovery of body weight and a significantly decreased number of ulcers in the caecum, and the ulcers in the colon had completely disappeared bythe end of the experiment. There was a good correlation found between the number of ulcers in the caecum and the bleeding scores of occult blood in faeces. The findings indicate that both conjugates were sufficiently delivered to the large intestine without deconjugation and that the lower dose of 5-ASA-CDCA is enough for treatment of ulcerative colitis in colonic inflammatory bowel diseases.

A Case with Micromegakaryocytes.

UNLABELLED: A boy with no previous history of bleeding presented with ecchymoses and splenomegaly. He was followed up for thrombocytopenia and micromegakaryocytes for 20 months till clinically malignancy was diagnosed. Micromegakaryocytes must always be treated with suspicion, as they may provide an important clue for dyshematopoesis. KEY WORDS: Micromegakaryocytes, Leukemia, Dismegakaryopoesis.

Congenital dyserythropoietic anemia type I with ringed sideroblasts.

A 25-year-old male with anemia, jaundice and liver dysfunction was admitted to our institution. Anisopoikilocytosis with tear-drop forms, polychromasia, basophilic stippling in peripheral blood smear, erythroid hyperplasia with megaloblastoid changes, binucleated cells and intranuclear bridging in bone marrow aspirate and spongy, unevenly condensed nuclear chromatin in electron microscopy studies indicated that he had congenital dyserythropoietic anemia (CDA) type I. As a rare finding in CDA, ringed sideroblasts were noted. It is proposed that this patient is an example for the designation 'variant congenital dyserythropoietic anemia with ringed sideroblasts'.

Detection of t(14;18) in turkish follicular lymphomas using the polymerase chain reaction.

A t(14;18) translocation is closely associated with the follicular lymphoma but is also seen in diffuse B cell lymphomas with a previous history of a follicular lymphoma as well as de novo diffuse lymphomas. Estimation of the frequency of t(14;18) in follicular lymphoma vary widely from 33 to 89%. Furthermore, no extensive data have been published on the frequency of t(14;18) in Turkish cases of follicular lymphoma. Representative tissue blocks from 67 patients with follicular lymphoma, 12 cases of diffuse large B cell lymphomas and 11 cases of reactive hyperplasias were examined for the presence of this translocation using PCR. DNA probes capable of detecting rearrangement at both the major and minor break point regions were employed. We could detect t(14;18) in 46 out of 67 cases (68.7%) of follicular and 25% of diffuse large B cell lymphomas. In follicular lymphomas 64.2% of these break points were at mbr and 4.5% were at the mcr region. Review of the literature showed that comparable results have been obtained previously using molecular techniques. Our data showed that despite the relative infrequency of follicular lymphomas in the Turkish population these lymphomas share a common molecular pathogenesis with involvement of bcl-2 gene and background incidence of such rearrangement is similar in all populations, regardless the incidence of folicular lymphoma.

Magnetic resonance imaging of bone marrow versus bone marrow biopsy in malignant lymphoma.

Bone marrow involvement is a frequent finding in malignant lymphoma. Bone marrow biopsy of the posterior iliac crest is routinely performed for staging. Abnormal magnetic resonance imaging (MRI) signals of bone marrow was also reported to be indicative of bone marrow involvement. This study included 60 patients with malignant lymphoma. Unilateral bone marrow biopsy of the posterior iliac crest was performed. MRI of lumbar spine was studied within 24 hours of bone marrow biopsy. 22 healthy controls were used for the detection of MRI objectivity during visual evaluation. In 83% of patients (50/60), biopsy and MRI results agreed completely. In two patients, histologic sections failed to show any evidence of bone marrow involvement despite abnormal MRI signals suggestive of involvement. In three patients, MRI was completely normal despite biopsy proven bone marrow infiltration. False negativity (3/60) and false positivity (2/60) rates were very low. Negative biopsy findings with positive or equivocal MRI results should not exclude bone marrow involvement and needs further evaluation with bilateral or guided biopsy. Thus, we conclude that MRI of bone marrow is a fairly sensitive, noninvasive modality and might be of potential value in detecting bone marrow infiltration in malignant lymphoid neoplasms which can be utilized as a useful adjunct to standard staging procedures.

Primary splenic tuberculosis in a patient with nasal angiocentric lymphoma: mimicking metastatic tumor on abdominal CT.

Tuberculosis may be difficult to diagnose when it presents in an uncommon extrapulmonary site. The authors report a case of splenic tuberculosis mimicking metastatic tumor on computed tomography in a 60-year-old woman who had been treated with combination chemotherapy for nasal angiocentric lymphoma. Diagnostic splenectomy revealed multiple necrotic masses in the spleen, which were consistent with caseating granulomas microscopically. Diagnosis was confirmed by positive cultures in Lowenstein medium, which grew typical Mycobacterium tuberculosis organisms. Following splenectomy, the patient was also treated with a triple-drug antituberculosis regimen with no recurrence of her symptoms.

Calciphylaxis: a condition mimicking necrotizing vasculitis.

A patient with end stage renal disease developed ischaemic skin necrosis and digital gangrene. He had diffuse arterial calcification associated with hyperparathyroidism secondary to renal failure. The patient received inappropriate cyclophosphamide therapy as he had been misdiagnosed as having an inflammatory vasculitis. This clinical picture, previously named "calciphylaxis" should come into the differential diagnosis of systemic vasculitis in a uraemic patient with hyperparathyroidism.

Thermodynamic characterization of drug binding to human serum albumin by isothermal titration microcalorimetry.

Binding sites on human serum albumin (HSA) for anionic drugs and fatty acids have been thermodynamically characterized by microcalorimetry. The binding and the thermodynamic parameters were directly computed from the calorimetric titration data at 37 degrees C in a phosphate buffer (pH 7.4) using one- and two-class binding models. From compensation analyses plotting the molar enthalpy change (delta Hm,i) versus those of the molar free energy (delta Gm,i) and molar entropy (delta Sm,i) for each class of binding sites, HSA binding sites were classified into groups S1, S2, and S3. Group S1 included high-affinity binding sites for site II-bound drugs, such as ibuprofen, flufenamic acid, and ethacrynic acid, and short- or medium-length alkyl-chain fatty acids; group S2 included low-affinity binding sites of site II-bound drugs and long-length alkyl-chain fatty acids; and group S3 contained the high-affinity binding sites for site I-bound drugs, such as phenylbutazone, oxphenbutazone, and warfarin, and long-length alkyl-chain fatty acids. High- and low-affinity bindings sites for salicylic acid and acetylaslicylic acid agreed with the regions of groups S3 and S2, respectively. Groups S1 and S2 were characterized by large negative values of delta Hm,i and delta Sm,i, reflecting van der Waals interaction and hydrogen-bonding formation in low dielectric media, and the main force to stabilize the binding complex in group S3 was a hydrophobic interaction, characterized by a small negative delta Hm,i and minor or positive values of delta Sm,i (entropy-driven).

Biothermodynamic characterization of monocarboxylic and dicarboxylic aliphatic acids binding to human serum albumin: a flow microcalorimetric study.

Thermodynamic parameters have been evaluated for the binding of unbranched monocarboyxlic aliphatic acids (MCAs) of 4 to 16 carbons (MC4 to MC16) and dicarboxylic aliphatic acids (DCAs) of 4 to 16 carbons (DC4 to DC16) to human serum albumin (HSA) on the basis of microcalorimetric measurement at pH 7.4 and 37 degrees C by computer-fitting to single- and two-class binding models. Long-chain MCAs (MC10 to MC16) and DCAs (DC14 and DC16) had the first class of binding sites with high affinity (large binding constant) of 10(5) to 10(6) M-1 and the second class with lower affinity and high capacity (large numbers of binding sites). Short- or medium-chain MCAs and DCAs bound to HSA at some low affinity binding sites. The binding constants of MCAs were ten times larger than those of DCAs. All the relationships between the thermodynamic parameters and alkyl-chain length of the acids showed clear-cut inflections in their plots around eight or nine methylene units. The free energy change of the first class of binding sites (- delta G1) became more negative with an increment of -1.0 kJ mol-1 CH2(-1) as the alkyl-chain length increased, but there were steep rises between MC9 and MC11 with -2.90 kJ mol-1 CH2(-1) and between DC9 and DC12 with -2.02 kJ mol-1 CH2(-1). The enthalpy change (- delta H) increased at the rate of -7.4 kJ mol-1 CH2(-1) to the maximum at MC9 and DC10, then decreased due to hydrophobicity of the alkyl-chains. From compensation analyses (delta H vs. delta S and delta G), HSA binding sites were characterized into three groups.

Thermodynamic aspects of fatty acids binding to human serum albumin: a microcalorimetric investigation.

Thermodynamic parameters have been evaluated for the binding interaction between human serum albumin (HSA) and unbranched fatty acids (FFA) on the basis of a flow microcalorimetric measurement at pH 7.4 and 37 degrees C by computer-fitting to single- and two-class binding models. The heat of binding increased exothermically with increasing alkyl chain length. FFA with nine or less carbons bound to only one class of binding sites (n = 2) with a binding constant (K) of 10(4) M-1. FFA with ten or more carbons bound to the first class of binding sites with high affinity K in the older of 10(5) to 10(6) M-1, and to the second class with a lower affinity and high capacity. The free energy change of the first class of binding sites (delta G1) became more negative as the chain length of FFA was increased. The enthalpy change per mol of FFA (delta H) decreased at the rate of -7.47 kJ.mol-1.CH-1(2) to a minimum at C9 and then increased due to the hydrophobicity of alkyl chains. Compensation analysis for the i th class of HSA molecule by plotting molar changes of enthalpy (delta Hmi) against entropy (delta Smi) and free energy (delta Gmi) indicates two distinct binding sites. The first class (i = 1) of the long-chain FFA on HSA is an entropy-driven reaction associated with nearly constant values of delta Hm1 (-43.0 +/- 4.8 kJ.mol-1), slightly negative values of delta Sm1 (-47.4 less than or equal to delta Sm1 less than or equal to -8.1 J.mol-1.K-1) and -delta Gm1 values, increasing with increasing alkyl chain length. The second class (i = 2) of the long-chain FFA may lie in the same region as the binding sites of the short- and medium-chain FFA with a linear relationship between delta Hmi-delta Smi.