Exposure to foreign gut microbiota can facilitate rapid dietary shifts.

Dietary niche is fundamental for determining species ecology; thus, a detailed understanding of what drives variation in dietary niche is vital for predicting ecological shifts and could have implications for species management. Gut microbiota can be important for determining an organism's dietary preference, and therefore which food resources they are likely to exploit. Evidence for whether the composition of the gut microbiota is plastic in response to changes in diet is mixed. Also, the extent to which dietary preference can be changed following colonisation by new gut microbiota from different species is unknown. Here, we use Drosophila spp. to show that: (1) the composition of an individual's gut microbiota can change in response to dietary changes, and (2) ingestion of foreign gut microbes can cause individuals to be attracted to food types they previously had a strong aversion to. Thus, we expose a mechanism for facilitating rapid shifts in dietary niche over short evolutionary timescales.

Influence of transducer frequency and imaging modality on the intraoperative assessment of myocardial perfusion with transesophageal echocardiography.

OBJECTIVE: To determine factors that improve intraoperative myocardial perfusion assessment with conventional ultrasound imaging and intravenous ultrasound agents. DESIGN: Prospective cohort study with repeated interventions on each patient. SETTING: Single university hospital. PARTICIPANTS: Fourteen patients scheduled for elective coronary artery bypass graft surgery. INTERVENTIONS: Myocardial perfusion was evaluated with contrast transesophageal echocardiography during conventional imaging after central venous injections of the contrast agent Optison (0.3 mL) before cardiopulmonary bypass. Eight patients received the injection during continuous sampling at each of 4 transducer frequency settings (3.5, 5.0, 6.0, 7.0 MHz). In another 6 patients, injections were administered during continuous and intermittent sampling (electrocardiogram-gated) at 3.5 and 5.0 MHz. Generalized estimating equations were used to compare mean responses, with p < or = 0.05 considered significant. MEASUREMENTS AND MAIN RESULTS: All recorded images were analyzed with off-line videodensitometry. Background-corrected peak pixel intensity (PPI(corr)) and rate of change in pixel intensity (PPI(corr)/T(PPI)) were determined for each injection. PPI(corr) was greater at 3.5 MHz than at 5.0, 6.0, and 7.0 MHz (p < 0.001). PPI(corr)/T(PPI) was greater at 3.5 MHz than at 5.0 (p < 0.001), 6.0 (p = 0.003), and 7.0 MHz (p < 0.001). PPI(corr) was greater for gated than for nongated sampling conditions at 3.5 (p < 0.05) and 5.0 MHz (p < 0.05). CONCLUSION: To optimize myocardial contrast opacification, intraoperative transesophageal echocardiography should be performed with intermittent sampling at a transducer frequency close to the intrinsic frequency of the contrast agent.

Photodynamic therapy-mediated oxidative stress as a molecular switch for the temporal expression of genes ligated to the human heat shock promoter.

Oxidative stress associated with photodynamic therapy (PDT) is a transcriptional inducer of genes encoding stress proteins, including those belonging to the heat shock protein (hsp) family. The efficiency of PDT to function as a molecular switch by initiating expression of heterologous genes ligated to the human hsp promoter was examined in the present study. Selective and temporal reporter gene expression was documented after PDT in mouse radiation-induced fibrosarcoma cells stably transfected with recombinant vectors containing an hsp promoter ligated to either the lac-z or CAT reporter genes and in transfected radiation-induced fibrosarcoma tumors grown in C3H mice. Hyperthermia treatments were included as a positive control for all experiments. Expression vectors containing either human p53 or tumor necrosis factor (TNF)-alpha cDNA under the control of an hsp promoter were also constructed and evaluated. A p53 null and TNF-alpha-resistant human ovarian carcinoma (SKOV-3) cell line was stably transfected with either the p53 or TNF-alpha constructs. Inducible expression and function of p53 as well as inducible expression, secretion, and biological activity of TNF-alpha were documented after PDT or hyperthermia in transfected SKOV cells. These results demonstrate that PDT-mediated oxidative stress can function as a molecular switch for the selective and temporal expression of heterologous genes in tumor cells containing expression vectors under the control of an hsp promoter.

Further data on the structure of brown seaweed fucans: relationships with anticoagulant activity.

The composition, molecular weight (MW), anticoagulant activity and nuclear magnetic resonance spectra of various low-molecular-weight fucans (LMWFs) obtained by partial hydrolysis or radical depolymerization of a crude fucoidan extracted from the brown seaweed Ascophyllum nodosum are compared. Fucose units were found mainly sulfated at O-2, to a lesser extent at O-3, and only slightly at O-4, contrary to previously published results for fucoidans from other brown seaweeds, and fucose 2, 3-O-disulfate residues were observed for the first time. As the sulfation pattern excluded an alpha-(1-->2)-linked fucose backbone and a high proportion of alpha-(1-->4) linkages was found, it would appear that the concept of fucoidan structure needs to be revised. Anticoagulant activity is apparently related not only to MW and sulfation content, as previously determined, but also (and more precisely) to 2-O-sulfation and 2,3-O-disulfation levels.

Spiral CT of acute pulmonary thromboembolism: evaluation of pleuroparenchymal abnormalities.

PURPOSE: The goal of this work was to identify and categorize the spectrum of pulmonary parenchymal and pleural abnormalities identified by CT in patients with acute pulmonary thromboembolism (PE). METHOD: A review of interpretations from 4,715 consecutive contrast-enhanced thoracic CT studies identified 41 examinations in which the diagnosis of PE was reported. Thirty-four studies were available for review, and two radiologists confirmed intraluminal defects in 31 patients. The number of emboli were counted and localized using bronchopulmonary nomenclature. Associated parenchymal and pleural abnormalities were tabulated. RESULTS: Of the 31 patients, 13 underwent confirmatory or correlative studies including angiography, radionuclide study, or autopsy. In addition, deep venous thrombosis was confirmed by ultrasound or MRI in 13 patients. An average of 7.5 emboli per patient was detected. Pleuroparenchymal findings were as follows: Nine patients (29%) had no acute pulmonary parenchymal or pleural abnormality. In the remaining 22 patients, pleural effusion was the most common abnormality, found in 14 of 31 (45%). Ten patients (32%) had peripheral wedge-shaped parenchymal opacities suggestive of pulmonary infarction. Normally enhancing lobar atelectasis was seen in nine patients (29%). Six patients (19%) demonstrated heterogeneous parenchymal enhancement within nonaerated lung, two of whom had pathologically proven pulmonary infarct. Thirteen of 31 patients underwent high resolution CT; a typical mosaic perfusion pattern was seen in only 1 patient. CONCLUSION: Twenty-nine percent of patients with acute PE had no acute lung parenchymal abnormality on CT; thus, the absence of parenchymal abnormality on CT does not exclude PE. High resolution CT mosaic perfusion was not a common feature of acute pulmonary embolism. Regions of decreased enhancement within nonaerated lung, seen in 19%, may prove to be an indicator of pulmonary infarction; however, this is a nonspecific finding.

Photodynamic therapy sensitivity is not altered in human tumor cells after abrogation of p53 function.

Photodynamic therapy (PDT) is an effective local cancer treatment that induces cytotoxicity through the intracellular generation of reactive oxygen species. The current study investigated whether abrogation of wild-type p53 expression modified the sensitivity of tumor cells to PDT-mediated oxidative stress. In these experiments, human colon (LS513) and breast (MCF-7) carcinoma cells exhibiting a wild-type p53 phenotype were directly compared to LS513 and MCF-7 cells with abrogated p53 function induced by stable integration of the human papillomavirus type 16 E6 viral oncoprotein. The effectiveness of this viral oncoprotein to target p53 for degradation was confirmed using a p53 transactivation reporter gene assay. Western analysis also confirmed attenuated expression of p53 in E6-transfected cells. Photosensitivity of PDT-treated cells was measured by a clonogenic assay and found to be equivalent for parental and p53-abrogated cells. PDT-mediated oxidative stress resulted in a rapid shift of pRb from a hyperphosphorylated form to a predominantly underphosphorylated form in parental cells that was not preceded by increases in p53 or p21 expression. Hypophosphorylated pRb was also observed in PDT-treated LS513/E6 and MCF-7/E6 cells, further indicating that p53 was not involved in this process. Delayed expression of p53 and p21 proteins was seen in parental cells 24-48 h after photosensitization. Cell cycle analysis showed that the abrogation of p53 had minimal effects on an observed PDT-induced G1 block. Rapid induction of apoptosis was documented in PDT-treated LS513 cells, whereas LS513/E6 treated cells exhibited reduced apoptosis in response to PDT. The MCF-7 cell lines exhibited a minimal apoptotic response to PDT. These results indicate that p53 expression does not directly modulate tumor cell sensitivity to PDT in either apoptosis-responsive (LS513) or nonresponsive (MCF-7) cells.

A familial case of X chromosome deletion ascertained by cytogenetic screening of women with premature ovarian failure.

The association between X chromosome deletions and premature ovarian failure is well established. Previous anecdotal reports however, have not documented the prevalence of X deletions in women with premature ovarian failure. We therefore performed cytogenetic analyses on 79 women with primary or secondary amenorrhoea to assess the utility of screening for a genetic marker for familial premature ovarian failure. A normal karyotype was found in 77 women. One woman with primary amenorrhoea had an XY karyotype and a woman with secondary amenorrhoea had a deletion at Xq 26.1. This second case had a family history of premature ovarian failure, and her mother who underwent premature ovarian failure at 28 years shared this deletion. The early diagnosis of familial X deletions causing premature ovarian failure allowed for the prediction of impending menopause and the implementation of manoeuvres to advance conception. Although cytogenetic aberrations are rare in secondary amenorrhoea, the ability to predict premature ovarian failure can be vital.

Preventing lead poisoning and its consequences.

The harmful effects of lead poisoning have been clearly espoused in the literature. All health care providers should be aware of these dangers and of current recommendations for screening for lead poisoning risks and follow-up of blood lead levels. Health education is an important aspect of health care. Pediatric nurses need to understand the hazards of lead poisoning, screening and follow-up recommendations, and have information about lead poisoning and abatement procedures available to families.

Increased soft-tissue blood flow in patients with reflex sympathetic dystrophy of the lower extremity revealed by power Doppler sonography.

OBJECTIVE: We evaluated the ability of power Doppler sonography to show increased soft-tissue blood flow in patients with reflex sympathetic dystrophy of the lower extremity. SUBJECTS AND METHODS: Power Doppler sonography was performed in 30 patients with reflex sympathetic dystrophy of the lower extremity and in 26 asymptomatic control subjects. The bilateral power Doppler sonograms that were obtained of the soft tissues of the dorsum of the foot of each subject were grouped in pairs, and three sonologists who were unaware of clinical information independently reviewed the images. Images were evaluated for the amount of power Doppler signal shown on the following scale: 1 = no flow or minimal flow; 2 = mild flow; 3 = moderate flow; and 4 = marked flow. RESULTS: More power Doppler flow was seen in the patients with reflex sympathetic dystrophy than in the control subjects (p < .005). In addition, side-to-side asymmetry of flow was seen in patients, but this trend was not statistically significant (p < .20). Receiver operating characteristic (ROC) analysis showed that combined flow and asymmetry were more related to reflex sympathetic dystrophy than either parameter alone (area under the ROC curve: for flow, 0.748; for asymmetry, 0.566; for both, 0.799). We found that when the sum of power Doppler flow in both feet was greater than or equal to five, and asymmetry of flow was greater than or equal to one, the sensitivity of power Doppler sonography for reflex sympathetic dystrophy was 73% and the specificity was 92%. CONCLUSION: Patients with reflex sympathetic dystrophy of the lower extremity have increased power Doppler flow compared with asymptomatic control subjects. Patients may also exhibit more side-to-side asymmetry of flow than control subjects.

Distal 6p deletion syndrome: a report of a case with anterior chamber eye anomaly and review of published reports.

We describe a 32 year old male with a distal 6p24.3-->pter deletion. He has specific developmental anomalies of the anterior chamber of the eye and a cleft uvula which is consistent with the recent localisation of genes for iris development and orofacial clefting to distal 6p. In addition he has progressive sensorineural deafness and this may localise a gene for deafness to this region. We conclude that a refined distal 6p deletion syndrome exists and includes a characteristic facial appearance with hypertelorism, downward slanting palpebral fissures, tented mouth, smooth philtrum, palatal malformation, ear anomalies, anterior chamber eye defects, progressive sensorineural deafness, cardiac defects, abdominal herniae, small external genitalia, and motor and speech delay.

Differential photosensitivity in wild-type and mutant p53 human colon carcinoma cell lines.

Tumor sensitivity to cancer therapies may be modulated by the p53 status of the malignant cells. Generally, tumors retaining wild-type p53 are more sensitive to radiotherapy and some chemotherapeutic agents than are tumors with either a mutated or deleted p53 phenotype. The role of p53 in the responsiveness to PDT as a cancer treatment is clinically unknown. In the current study, we evaluated the photosensitivity of two human colon carcinoma cell lines, one expressing wild-type p53 protein and the other expressing mutant p53. Wild-type p53 cells were found to be significantly more sensitive to Photofrin-mediated photodynamic treatment measured by clonogenic assay. Uptake of the photosensitizer was equivalent for both cell lines. Interestingly, sensitivity of the colon carcinoma cell lines to ionizing radiation was similar. These two cell lines represent a useful model for examining p53 involvement in the cellular response to PDT-mediated oxidative stress.

Inv(10)(p11.2q21.2), a variant chromosome.

We present 33 families in which a pericentric inversion of chromosome 10 is segregating. In addition, we summarise the data on 32 families in which an apparently identical inv(10) has been reported in the literature. Ascertainment was through prenatal diagnosis or with a normal phenotype in 21/33 families. In the other 12 families, probands were ascertained through a wide variety of referral reasons but in all but one case (a stillbirth), studies of the family showed that the reason for referral was unrelated to the chromosome abnormality. There has been, to our knowledge, no recorded instance of a recombinant chromosome 10 arising from this inversion and no excess of infertility or spontaneous abortion among carriers of either sex. We propose that inv(10)(p11.2q21.2) can be regarded as a variant analogous to the pericentric inversion of chromosome 2(p11q13). We conclude that prenatal chromosome analysis is not justified for inv(10) carriers. In addition, family investigation of carrier status is not warranted in view of the unnecessary concern this may cause parents and other family members.

Centromeric inactivation in a dicentric human Y;21 translocation chromosome.

A de novo dicentric Y;21 (q11.23;p11) translocation chromosome with one of its two centromeres inactive has provided the opportunity to study the relationship between centromeric inactivation, the organization of alphoid satellite DNA and the distribution of CENP-C. The proband, a male with minor features of Down's syndrome, had a major cell line with 45 chromosomes including a single copy of the translocation chromosome, and a minor one with 46 chromosomes including two copies of the translocation chromosome and hence effectively trisomic for the long arm of chromosome 21. Centromeric activity as defined by the primary constriction was variable: in most cells with a single copy of the Y;21 chromosome, the Y centromere was inactive. In the cells with two copies, one copy had an active Y centromere (chromosome 21 centromere inactive) and the other had an inactive Y centromere (chromosome 21 centromere active). Three different partial deletions of the Y alphoid array were found in skin fibroblasts and one of these was also present in blood. Clones of single cell origin from fibroblast cultures were analysed both for their primary constriction and to characterise their alphoid array. The results indicate that (1) each clone showed a fixed pattern of centromeric activity; (2) the alphoid array size was stable within a clone; and (3) inactivation of the Y centromere was associated with both full-sized and deleted alphoid arrays. Selected clones were analysed with antibodies to CENP-C, and staining was undetectable at both intact and deleted arrays of the inactive Y centromeres. Thus centromeric inactivation appears to be largely an epigenetic event.

Increased photosensitivity in HL60 cells expressing wild-type p53.

Loss of p53 function has been correlated with decreased sensitivity to chemotherapy and radiation therapy in a variety of human tumors. Comparable analysis of p53 status with sensitivity to oxidative stress induced by photodynamic therapy has not been reported. In the current study we examined photosensitivity in human promyelocytic leukemia HL60 cells exhibiting either wild-type p53, mutated p53 or deleted p53 expression. Experiments were performed using a purpurin, tin ethyl etiopurpurin (SnET2)-, or a porphyrin, Photofrin (PH)-based photosensitizer. Total SnET2 accumulation was comparable in all three cell lines. Uptake of PH was highest in cells expressing wild-type p53 but incubation conditions could be adjusted to achieve equivalent cellular PH levels during experiments that analyzed photosensitivity. Survival measurements demonstrated that HL60 cells expressing wild-type p53 were more sensitive to PH- and SnET2-mediated photosensitization, as well as to UVC irradiation, when compared to HL60 cells exhibiting deleted or mutated p53 phenotypes. A rapid apoptotic response was observed following purpurin- and porphyrin-induced photosensitization in all cell lines. Results of this study indicate that photosensitivity is increased in HL60 cells expressing wild-type p53 and that photosensitizer-mediated oxidative stress can induce apoptosis through a p53-independent mechanism in HL60 cells.

MR imaging in male infertility.

In patients with male infertility, endorectal magnetic resonance (MR) imaging provides high-resolution images of the prostate gland and ejaculatory apparatus. The multiplanar capability of MR imaging allows production of a detailed map of the reproductive tract for guiding treatment. Causes of male infertility can be classified as congenital, acquired, infectious, or hormonal. Wolffian duct abnormalities include agenesis of the kidney, vas deferens, or seminal vesicle and cysts of the vas deferens, seminal vesicle, or urogenital sinus-ejaculatory duct. Müllerian duct abnormalities are less common and consist of müllerian duct cysts and utricle cysts. Cowper duct cysts and peripheral-zone prostatic cysts are acquired causes of male infertility. Prostatitis, an infectious cause of male infertility, may mimic carcinoma on long repetition time/echo time images. A low testosterone levels is one of the hormonal causes of male infertility. Pitfalls in the interpretation of MR images can be avoided by familiarity with normal and abnormal findings in patients with male infertility.

RDCI, the vasoactive intestinal peptide receptor: a candidate gene for the features of Albright hereditary osteodystrophy associated with deletion of 2q37.

Albright hereditary osteodystrophy (AHO) is an autosomal dominant disorder characterised by the presence of brachymetaphalangism, short stature, obesity, and mental retardation. Variable biochemical changes many represent either pseudohypoparathyroidism (PHP) owing to resistance to parathormone (PTH) or pseudopseudohypoparathyroidism (PPHP) with no hormone resistance. In most cases of AHO, reduced levels of Gs alpha have been found and a number of deactivating mutations in the gene for Gs alpha located on chromosome 20q13 have been described. Recently a number of people with an AHO-like phenotype have been reported in whom a deletion of chromosomal region 2q37 has been found in the absence of biochemical abnormalities or a reduction in Gs alpha activity. We present a further female patient with a cytogenetically visible deletion of 2q37, an AHO-like phenotype, and unusual biochemistry suggesting moderate PTH resistance. The vasoactive intestinal peptide receptor (RDCI) has recently been mapped to 2q37 and we propose that this is a candidate gene, hemizygosity of which affects signal transduction and leads to the AHO-like phenotype found in patients with 2q37 deletions.

Cellular targets and molecular responses associated with photodynamic therapy.

The positive clinical results associated with photodynamic therapy (PDT) have led to an expanded need to identify the cellular targets and molecular responses associated with this treatment. Increased knowledge regarding the mechanisms of action associated with PDT-mediated cytotoxicity should contribute to the continued advancement of this therapy. This report focuses on recent studies analyzing PDT resistance and examining stress protein and early response gene activation induced by photosensitizer mediated oxidative stress. Recurring observations from these studies indicate that subcellular targets and cellular responses associated with PDT can vary significantly for different photosensitizers.