Diet and irritable bowel syndrome: an update from a UK consensus meeting.

There has been a renewed interest in the role of dietary therapies to manage irritable bowel syndrome (IBS), with diet high on the agenda for patients. Currently, interest has focussed on the use of traditional dietary advice (TDA), a gluten-free diet (GFD) and the low FODMAP diet (LFD). A consensus meeting was held to assess the role of these dietary therapies in IBS, in Sheffield, United Kingdom.Evidence for TDA is from case control studies and clinical experience. Randomised controlled trials (RCT) have demonstrated the benefit of soluble fibre in IBS. No studies have assessed TDA in comparison to a habitual or sham diet. There have been a number of RCTs demonstrating the efficacy of a GFD at short-term follow-up, with a lack of long-term outcomes. Whilst gluten may lead to symptom generation in IBS, other components of wheat may also play an important role, with recent interest in the role of fructans, wheat germ agglutinins, as well as alpha amylase trypsin inhibitors. There is good evidence for the use of a LFD at short-term follow-up, with emerging evidence demonstrating its efficacy at long-term follow-up. There is overlap between the LFD and GFD with IBS patients self-initiating gluten or wheat reduction as part of their LFD. Currently, there is a lack of evidence to suggest superiority of one diet over another, although TDA is more acceptable to patients.In view of this evidence, our consensus group recommends that dietary therapies for IBS should be offered by dietitians who first assess dietary triggers and then tailor the intervention according to patient choice. Given the lack of dietetic services, novel approaches such as employing group clinics and online webinars may maximise capacity and accessibility for patients. Further research is also required to assess the comparative efficacy of dietary therapies to other management strategies available to manage IBS.

Clinical study on the effects of a cosmetic product on dermal extracellular matrix components using a high-resolution multiphoton tomograph.

BACKGROUND/PURPOSE: The aim of this study was to demonstrate the effects of selected plant extracts in a cosmetic cream on the dermal network components after a 3-month treatment using an in vivo multiphoton tomographic device. METHODS: Twenty-four Caucasian women aged between 45 and 65 applied randomly a cosmetic emulsion B containing active ingredients (soy and jasmine) twice a day on one arm and its vehicle A (without active ingredients) on the other arm during 3 months. Measurements were performed on the internal side of the forearm before starting the treatment (T0), after 4 week (T4) and 12 weeks (T12) treatment. Measurements consisted of a multi-layers acquisitions using a multiphoton tomograph with subcellular resolution. Optical sections (about 6 microm thick) were recorded from 0 to about 200 microm using two different wavelengths: 760 and 820 nm. To compare the series of images and obtain an objective quantification of the signal of second harmonic generation (SHG) and autofluorescence, the method used consisted of taking the integrated brightness of an image (same rectangular area for all images) as a measure of the signal. Following this step, a ratio between brightness of images from the area treated with cream A or B and brightness of untreated area was calculated and used as an assessment of treatment efficacy. The parameter used for statistical analysis (variance analysis) is the difference before and after 12 weeks of treatment by either cream A or B of the signal ratios calculated in the upper dermis (118-130 microm) and those from a deeper region of the upper dermis (165-178 microm). RESULTS: Signals (autofluorescence+SHG) of extracellular matrix do not change significantly with time (weeks 0, 4 and 12) when cream A (vehicle with no active ingredient) is applied. Treatment with cream B results in an enhancement in the signal level of extracellular matrix at week 12. The comparison of signals, in both areas (118-130 microm and 160-178 microm), show an higher increase in the deeper region than in the more superficial one for product B while we do not notice any change with product A. CONCLUSION: The multiphoton tomograph provided excellent high-resolution images, which describe clearly the different skin layers, single cells and extracellular matrix components in all the 24 volunteers. Statistic analyses reveal a real effect for product B with selected plant extracts, known to increase collagen synthesis. Changes observed are characteristics of modifications in dermal collagen and elastin content. To our knowledge, it is the first time that it was possible to demonstrate in vivo the effect of a cosmetic product on the superficial dermal layer, in a non-invasive and non-destructive process, i.e. without cutting the skin.

A chicken red cell inhibitor of transcription associated with the terminally differentiated state.

When a red cell nuclear extract (RCE) from adult chickens was injected into Xenopus oocytes along with the chicken beta globin gene, transcript levels were dramatically reduced compared to injection of DNA alone. The inhibitory action of the RCE was not specific to the beta globin gene since the Herpes thymidine kinase and Xenopus 5S RNA gene transcript levels were similarly reduced. Transcriptional repression was observed even after passage of the RCE through oocyte cytoplasm to the nucleus. The inhibitory activity binds to DNA cellulose, which suggests that the inhibitor either binds to DNA or associates with DNA-binding proteins. Nuclease digestion of the chromatin assembled on injected beta globin DNA revealed that inhibition was not associated with local changes in chromatin structure. Extracts from 9-d chicken embryonic erythroid cells, in which the endogenous beta globin gene is actively expressed, did not inhibit transcription. The inhibitory activity is, therefore, restricted to transcriptionally quiescent, adult erythrocytes. Since the inhibitory effects were seen with both polymerase II and III directed genes, we speculate that the activity may be part of the extreme transcriptional repression which occurs in the terminally differentiated erythrocyte.

Parathyroid hormone production in vitro by human parathyroid cells transformed by Simian virus 40.

Cells froma human parathyroid adenoma were infected with simian virus 40 and maintained through 13 subcultures in monolayer tissue culture. For more than 9 months, these "transformed" cells contimed to produce parathyroid hormone which was identified by radioimmunoassay and density-gradient ultra centrifugation.

Clinical two-photon microendoscopy.

Two-photon medical imaging has found its way into dermatology as an excellent method for noninvasive skin cancer detection without need of contrast agents as well as for in situ drug screening of topically-applied cosmetical and pharmaceutical components. There is an increasing demand to apply the multiphoton technology also for deep-tissue skin imaging as well as for intracorporal imaging. We report on the first clinical use of multiphoton endoscopes, in particular of a miniaturized rigid two-photon GRIN lens endoscope. The microendoscope was attached to the multiphoton tomograph DermaInspect and employed to detect the extracellular matrix proteins collagen and elastin in the human dermis of volunteers and patients with ulcera by in vivo second harmonic generation and in vivo two-photon autofluorescence.

Selective and rapid nuclear translocation of a c-Myc-containing complex after fertilization of Xenopus laevis eggs.

We report here unusual features of c-Myc specific to early embryonic development in Xenopus laevis, a period characterized by generalized transcriptional quiescence and rapid biphasic cell cycles. Two c-Myc protein forms, p61 and p64, are present in large amounts in the oocyte as well as during early development. In contrast, only p64 c-Myc is present in Xenopus somatic cells. p61 c-Myc is the direct translation product from both endogenous c-myc mRNAs and c-myc recombinant DNA. It is converted to the p64 c-Myc form after introduction into an egg extract, in the presence of phosphatase inhibitors. p61 and p64 belong to two distinct complexes localized in the cytoplasm of the oocyte. A 15S complex contains p64 c-Myc, and a 17.4S complex contains p61 c-Myc. Fertilization triggers the selective and total entry of only p64 c-Myc into the nucleus. This translocation occurs in a nonprogressive manner and is completed during the first cell cycles. This phenomenon results in an exceptionally high level of c-Myc in the nucleus, which returns to a somatic cell-like level only at the end of the blastulation period. During early development, when the entire embryonic genome is transcriptionally inactive, c-Myc does not exhibit a DNA binding activity with Max. Moreover, embryonic nuclei not only prevent the formation of c-Myc/Max complexes but also dissociate such preformed complexes. These peculiar aspects of c-Myc behavior suggest a function that could be linked to the rapid DNA replication cycles occurring during the early cell cycles rather than a function involving transcriptional activity.

Analysis of c-Myc and Max binding to the c-myc promoter: evidence that autosuppression occurs via an indirect mechanism.

c-myc negatively autoregulates its expression at the level of transcriptional initiation, although the precise mechanism remains debated. While conclusive evidence for c-Myc binding in its own promoter has not been found, it has been proposed that c-Myc binds to a site upstream of the human c-myc gene which may also be a component of a replication origin (Ariga et al., 1989). In an attempt to clarify this issue, sequences flanking the c-myc gene were screened for c-Myc or Max binding sites using a novel procedure to facilitate the detection of DNA binding dependent upon long distance interactions or DNA secondary structure. Since the sequence specificity of DNA binding proteins may also be mediated by interaction with other proteins or by protein modification, this affinity capture assay was used in conjunction with nuclear extracts, potentially allowing the selection of novel in vivo DNA binding specificities. Using conditions that gave strong binding to an internal control sequence, c-Myc or Max binding elements were not detected in genomic sequences extending 5.4 kb upstream of the Xenopus c-myc gene. Identical results were obtained using both purified proteins and a variety of nuclear extracts, suggesting c-myc autosuppression most likely involves an indirect pathway.

Site-directed mutagenesis studies on the binding of the globular domain of linker histone H5 to the nucleosome.

The globular domain of the linker histone H5 has been expressed in Escherichia coli. The purified peptide is functional as it permits chromatosome protection during micrococcal nuclease digestion of chromatin reconstituted with the peptide, indicating that it binds correctly at the dyad axis of the nucleosomal core particle. The globular domain residue lysine 64 is highly conserved within the linker histone family, and site-directed mutagenesis has been used to assess the importance of this residue in the binding of the globular domain of linker histone H5 to the nucleosome. Recombinant peptides mutated at lysine 64 are unable to elicit chromatosome protection to the same degree as the wild-type peptide, and since they appear to be fully folded, these observations confirm a major role for this residue in determining the effective interaction between the globular domain of histone H5 and the nucleosome.

Production of a functional full-length Xenopus laevis c-Myc protein in insect cells.

C-Myc is a nuclear phosphoprotein whose normal cellular function has not yet been clearly defined. Studies with this protein have always been constrained by the difficulty of obtaining full-length c-Myc in an active form, whatever the expression system used. We report here experimental conditions optimized to increase the solubility and the purification of c-Myc in a baculovirus expression system. Such conditions allow the production of both soluble and active full-length c-Myc. Interestingly, soluble c-Myc is found associated with a 500-kDa high-molecular-mass complex comparable to that found in human and Xenopus laevis embryos, and which may be required for its function in vivo.

Waldenström's macroglobulinaemia treated with cylophosphamide and chlorambucil.

A case of primary macroglobulinaemia of Waldenström is described in which prolonged treatment with the alkylating agents of cyclophosphamide and chlorambucil led to a sustained reduction in the concentration of circulating macroglobulin together with a concurrent improvement in the patient's symptoms.

Condom misuse among adolescents.

PIP: In the adolescent clinic of the Children's Center at the District of Columbia General Hospital, the proficiency of high-risk adolescents in condom usage was investigated. The majority of patients are served for sexually transmitted diseases (STDs), contraception, and the diagnosis of pregnancy. In December 1990 and March 1991, each teenager who visited the clinic was given a latex reservoir-tipped condom and the plastic cover of a 60 mL syringe and was instructed to place the condom on the plastic cover. Then each was asked if it is better to remove the condom while the penis is still hard (erect) or when it is soft (flaccid). A performance score was assigned to each subject based on the following variables: 1) pinch the reservoir tip, 2) orient the condom correctly (not inside out), 3) roll the condom down the shaft, and 4) know that condoms should be removed while the penis is still erect. The maximum performance score was 4 with 1 point awarded for each successfully completed component. 38 females and 19 males with an age range from 13 to 19 years were included in the study group. 3 males (15.8%) and 22 females (57.8%) were either treated or were receiving follow-up for an STD, for an overall STD rate of 43.9%. The mean performance score for the study population was 2.3. Females averaged a performance score of 2.34, versus 2.31 for males. Females with STDs averaged higher scores than females who were infection-free (2.4 versus 2.1). Conversely, males with STDs averaged lower scores than those without STDs (2.0 versus 2.4). The most common deficiency was the failure to pinch the reservoir tip (67%) followed by failure to remove the condom while the penis is erect (61%), incorrect (inside out) orientation (25%), and failure to roll the condom completely down the shaft (9%). Among adolescents, health-compromising sexual behavior continues. Health-care workers should provide information on sexuality issues such as genital tract infections and contraception.^ieng