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Caspase-2 triggers Bax-Bak-dependent and -independent cell death in colon cancer cells treated with resveratrol.

Polyphenol phytoalexin (resveratrol), found in grapes and red wine is a strong chemopreventive agent with promising safety records with human consumption and unique forms of cell death induction in a variety of tumor cells. However, the mechanism of resveratrol-induced apoptosis upstream of mitochondria is still not defined. The results from this study suggest that caspase-2 activation occurs upstream of mitochondria in resveratrol-treated cells. The upstream activation of caspase-2 is not dependent on its antioxidant property or NF-kappaB inhibition. The activated caspase-2 triggers mitochondrial apoptotic events by inducing conformational changes in Bax/Bak with subsequent release of cytochrome c, apoptosis-inducing factor, and endonuclease G. Caspase-8 activation seems to be independent of these events and does not appear to be mediated by classical death receptor processing or downstream caspases. Both caspase-2 and caspase-8 contribute toward the mitochondrial translocation of Bid, since neither caspase-8 inhibition nor caspase-2 inhibition could prevent translocation of Bid DsRed into mitochondria. Caspase-2 inhibitors or antisense silencing of caspase-2 prevented cell death induced by resveratrol and partially prevented processing of downstream caspases, including caspase-9, caspase-3, and caspase-8. Studies using mouse embryonic fibroblasts deficient for both Bax and Bak indicate the contribution of both Bax and Bak in mediating cell death induced by resveratrol and the existence of Bax/Bak-independent cell death possibly through caspase-8- or caspase-2-mediated mitochondria-independent downstream caspase processing.

Animals↗

Reiter's disease.

Explore the source record for details and available documents.

Adolescent↗

Oral prednisolone metasulphobenzoate in the treatment of active ulcerative colitis.

BACKGROUND: Corticosteroids are one of the mainstays of treatment for active ulcerative colitis, but they are associated with numerous side effects. The sparingly absorbed corticosteroid prednisolone metasulphobenzoate is used topically in the treatment of distal disease. A targeted-release oral preparation (Predocol) has been developed to allow delivery of this drug to the whole colon. We have studied the effect of oral Predocol on inflammation as measured by 99Tc(m)-HMPAO leucocyte scintigraphy in patients with symptomatic and sigmoidoscopic relapse of known extensive ulcerative colitis. METHODS: Fourteen patients were recruited and received Predocol 47.1 mg twice daily, 8 for 7 days and 6 for 14 days. Scintigraphy was performed prior to and at the end of treatment. Each segment of colon was graded (0-4) and individual scores summed to give a total scintigraphic score. RESULTS: Total scintigraphic score improved by a mean of 2.5 (P = 0.027). Mean individual scores improved in the rectum by 0.7 (P = 0.038) and in the descending colon by 0.8 (P = 0.033). CONCLUSIONS: Predocol is an oral preparation of a poorly absorbed salt of prednisolone that is effective in reducing inflammation over short treatment periods in patients with active ulcerative colitis.

Administration, Oral↗

Unusual case of non-exophytic invasive penile squamous cell cancer arising from a chronic sinus tract.

We present an unusual case of an extremely well-differentiated but deeply invasive squamous cell carcinoma of the penis without an obvious external lesion, arising from a chronic draining sinus tract. This case highlights how a confounding clinical history, physical examination and initial biopsies may lead to a significant delay in diagnosis. This delay may have resulted in tumour growth and the need for a more extensive partial penectomy than would have occurred had the diagnosis been made more promptly. Finally, this case demonstrates the key diagnostic utility of deep core biopsies of the penis in situations where a cutaneous lesion does not exist.

Adult↗

A randomized controlled trial to test an HIV-prevention intervention for Latino gay and bisexual men: lessons learned.

At the time of this writing, no randomized controlled trial (RCT) of an intervention to reduce unsafe sex among Latino gay and bisexual men (LGBM) had been published. We report the results of an RCT conducted in New York City in which 180 LGBM were assigned either to an intervention developed specifically for this population or to a wait-list control group. The intervention was based on empowerment theory and used factors identified in prior research as determinants of unsafe sex. By eligibility criteria, all men had engaged in unprotected anal intercourse (UAI) within two months of the baseline assessment. At first (two months) and second (six months later) follow-up assessments, approximately half of the men in the experimental group reported no UAI. Yet, a similar proportion of the control group also reported no UAI. Baseline data indicate that although the men had been the subject of social oppression and sexual prejudice (homophobia), they did not feel disempowered, externally controlled or fatalistic, and they reported self-efficacy and intentionality to enact safer sex. Lessons learned are discussed, as well as notes of caution for future research employing a similar conceptual framework.

Adolescent↗

Study on the energy and protein metabolism in horses.

The present study focused on energy and protein metabolism in pregnant and lactating mares, including the suckling and weaned growing horses, in order to determine feed availability, as also the energy and protein requirements. The authors found that the feeding diets, consisting of alfalfa hay, oats and compounds, had different availability values in terms of energy and protein, according to animal physiological conditions and age. Thus, the pregnant mares utilized the metabolizable energy (ME) and digestible crude protein (DCP) intake in average proportions of 64.5 +/- 3.2%, 54.6 +/- 3.0%, respectively, while in the lactating mares the values were 60.1 +/- 2.8%, respectively, 50.1 +/- 4.0%. However the amount of energy and protein required for maintenance was similar in these two animal physiological conditions: 531 kJ, ME/kg0.75, 529 KJ, ME/kg0.75 and 3 g DCP/kg0.75, respectively. The suckling colts had a daily average gain between 1405 and 891 g and the young horses after weaning up to 2 years of age between 773 and 447 g. The net efficiency of ME and of DCP for growth in the suckling colts was of 40.6 +/- 2.1% and 46.1 +/- 3.2%, respectively and in young horses after weaning had similar values of 40.3 +/- 4.0%, respectively 44.4 +/- 2.2%, but the maintenance requirement of energy and protein differed from 506 kJ, ME/kg0.75 and 4.51 g DCP/kg0.75 respectively to 587 kJ, ME/kg0.75 and 3.51 g DCP/kg0.75, respectively.

Animal Feed↗

Mixed Evidence that Dosage Sensitive Genes Drive Global Dosage Compensation in Flour Beetles.

Heteromorphic sex chromosomes create inherent gene dosage differences between males and females because one sex carries a single copy of the X chromosome while the other carries two. Many species have evolved mechanisms that equalize X-linked gene expression between the sexes and, in some cases, restore ancestral autosomal levels, a process known as dosage compensation. Although chromosome-wide compensation is common in male heterogametic (XY) insects, regulatory outcomes vary across taxa and sex chromosome systems, leaving the evolutionary forces shaping sex chromosome regulation unresolved. One hypothesis proposes that the extent to which genes are sensitive to changes in gene dose determines whether complete compensation evolves. We tested predictions of this insensitive sex chromosome hypothesis (ISCH) across five flour beetle species using comparative transcriptomics and genome-wide RNAi-derived measures of gene-by-gene sensitivity. Including an X-autosome fusion in Tribolium confusum allowed direct assessment of expression evolution following a transition from a diploid autosome to a hemizygous Neo-X. Across all five species, we detect complete chromosome-wide dosage compensation and balance between the sexes in somatic tissues, including the Neo-X region. Consistent with ISCH predictions, neither the ancestral Shared-X nor the Neo-X is depleted of genes that are sensitive to RNAi-based expression disruption. However, contrary to expectations, at the level of individual genes, we find little evidence that more sensitive genes exhibit reduced expression divergence. These results suggest that chromosome-wide compensation can be maintained by global regulatory mechanisms that persist through sex chromosome turnover, even when gene-by-gene constraints are weak. Understanding the molecular basis of these mechanisms remains a central challenge in sex chromosome evolution.

Animals↗

Molecular epidemiology of type 1 polioviruses isolated in Israel and defined by restriction fragment length polymorphism assay.

The genomic variability of 27 type 1 polioviruses (PV-1) isolated in Israel during 1980-1991 was examined by restriction fragment length polymorphism (RFLP) analysis of a reverse-transcribed genomic fragment amplified by polymerase chain reaction. By using the restriction enzymes HaeIII, DdeI, and HpaII, strain-specific restriction profiles were generated for the PV-1/Mahoney and PV-1/Sabin strains and 27 wild-type isolates. The profile observed for PV-1 isolated during an outbreak in 1988 was also observed for PV-1 isolated from different places in Israel in 1982 and 1983, 1987, and 1991. This profile, characterized by the lack of the DdeI site, was different from the DdeI profile of PV-1 isolated in 1984 or in 1986 from sporadic cases of poliomyelitis. The diversity of circulating PV-1 in Israel was also confirmed by nucleotide sequence analysis. The epidemiologic information provided by the RFLP and sequence data establishes a clear epidemiologic link between epidemic and sporadic virus strains and demonstrates the power of this molecular approach to epidemiology.

Base Sequence↗

Oxygen equilibrium and EPR studies on alpha1beta1 hemoglobin dimer.

We undertook this project to clarify whether hemoglobin (Hb) dimers have a high affinity for oxygen and cooperativity. For this, we prepared stable Hb dimers by introducing the mutation Trp-->Glu at beta37 using our Escherichia coli expression system at the alpha1beta2 interface of Hb, and analyzed their molecular properties. The mutant hybrid Hbs with a single oxygen binding site were prepared by substituting Mg(II) protoporphyrin for ferrous heme in either the alpha or beta subunit, and the oxygen binding properties of the free dimers were investigated. Molecular weight determination of both the deoxy and CO forms showed all these molecules to be dimers in the absence of IHP at different protein concentrations. Oxygen equilibrium measurements showed high affinity and non-cooperative oxygen binding for all mutant Hb and hybrid Hb dimers. However, EPR results on the [alpha(N)(Fe-NO)beta(M)(Mg)] hybrid showed some alpha1beta1 interactions. These results provide some clues as to the properties of Hb dimers, which have not been studied extensively owing to practical difficulties in their preparation.

Dimerization↗

Radiation damage induced by krypton ions in sintered alpha-Al2O3.

Alpha-alumina is a useful thermoluminescence (TL) dosemeter. The knowledge of its behaviour under irradiation is thus of primary importance. The purpose of this paper is to characterise the radiation damage produced by swift krypton ions using various experimental methods, namely TL, optical absorption, fluorescence and electron paramagnetic resonance (EPR). After ion irradiation, the TL intensity is shown to decrease, whereas the optical absorption rises in the whole studied wavelength range. These two phenomena seem to be related to one another. Furthermore, optical absorption measurements highlight the appearance of new absorption bands probably owing to oxygen vacancies. Induced defects are also observed in the EPR spectra of irradiated pellets. They are likely related to electronic holes trapped on oxygen ions. The concentration of these defects increases with ion fluence and fluorescence measurements indicate that some pre-existing defects such as F2(2+) centres follow the same trend up to approximately 4.1 x 10(13) ions cm(-2).

Aluminum Oxide↗

Antibiotic resistance patterns in nosocomial gram-negative bacterial infections in units with heavy antibiotic usage.

The pattern of antibiotic resistance amongst gram-negative bacteria (GNB) in paediatric units, which have heavy empirical usage of broad-spectrum antibiotics, was studied prospectively over a 6-month period. A total of 200 consecutive, non-duplicate gram-negative isolates were obtained from 109 patients admitted to intensive care and oncology units in two hospitals. The commonest isolates were Klebsiella spp (36.5 per cent) and Pseudomonas (20.0 per cent). The isolates showed lower susceptibility rates to the third-generation cephalosporins (47-62 per cent) compared with cefepime (91 per cent), imipenem (90 per cent) and ciprofloxacin (99 per cent). Fifty-four (52.8 per cent) Klebsiella and Escherichia coli isolates were determined to be extended-spectrum beta-lactamase (ESBL) producing strains. Antibiotics found to be effective against ESBL-producers were imipenem and ciprofloxacin. The high resistance rate amongst GNB to third-generation cephalosporins is a likely consequence of heavy empirical usage of this group of antibiotics. The carbapenems and quinolones remain useful agents in the management of patients admitted to these units.

Acinetobacter↗

Penile disorders in two paraplegics.

We present two rare cases of paraplegics with remarkable sequelae of the penis due to long-term usage of a condom-catheter. One involved hypertrophy of the glans prepuce, and the other had severe constriction of the distal portion of the corpus penis with two fistulae.

Adult↗

Auditory ERPs reveal brain dysfunction in infants with plagiocephaly.

It is suspected that the developmental delay in school-aged children diagnosed as infants suffering from plagiocephaly is caused by the modification of the skull form. To detect possible cognitive impairment in these children, we examined auditory ERPs to tones in infant patients. The infants with plagiocephaly exhibited smaller amplitudes of the P150 and the N250 responses to tones than healthy controls. Differences between the patients and control subjects indicate that already at this early age the presence of the plagiocephalic skull signals compromise of brain functioning. The present data suggest that most of the plagiocephalic infants have an elevated risk of auditory processing disorders. In the current study we demonstrated, for the first time, that the central sound processing, as reflected by ERPs, is affected in children with plagiocephaly.

Analysis of Variance↗

A case study of amnion rupture sequence with acalvaria, blindness, and clefting: clinical and psychological profiles.

The purpose of this article is to report the case of a 10-year-old girl born with anophthalmia, bilateral oblique facial clefts, and missing scalp and bones over the temporal and parietal areas of the cranial vault bilaterally. Early amnion rupture seems to be the most probable cause of this rare combination of anomalies. Because no similar case has been reported in the literature so far, we describe here the clinical and psychosocial history of this unusual patient, who has been able to live the intellectually and socially normal life of a blind child in spite of the major craniofacial deformities. The already completed and possible future therapeutic strategies are discussed.

Amniotic Band Syndrome↗

Maturation of the auditory event-related potentials during the first year of life.

This study examined the maturation of cortical auditory event-related potentials (ERPs) from birth until 12 months of age. In the 15 infants studied, all ERP peaks observable at 12 months of age, the P150, N250, P350, and N450 were identifiable already at birth, As in previous studies, the amplitudes of the ERP peaks increased and latencies shortened with increasing age. In addition, the time courses of the amplitude growth of these peaks differed from each other. It was concluded, that the generators of all the infantile ERP peaks are functional already at birth, and that the maturational changes in the waveform morphology can mostly be accounted for by the changing relative strengths of the different generators.

Acoustic Stimulation↗