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Biomedical subjects

J Stein

Publications and source records attributed to J Stein.

At least 199 records · Page 11Linked to original sources

Sexual abuse perpetrated by men with intellectual disabilities: a comparative study.

This paper compares cases of sexual abuse of adults with intellectual disabilities, reported across the South East of England, which were perpetrated by men with intellectual disabilities, with those committed by other male perpetrators. The comparison provides some support for the findings of other studies, which have suggested that men with intellectual disabilities offend against more male victims than non-disabled sex offenders and that their offences are somewhat less serious, but otherwise indicates common patterns of abusive behaviour across this divide but differential service responses and support for victims. So called 'peer abuse' is a widespread problem which service agencies have failed to address: repeated offences are frequent and lack of appropriate intervention is the norm.

Adult↗

Fact sheet: major causes of death in Canada, 1993-1995.

Mortality is one of many summary indicators of disease burden. The following tables and graphs display the relative contributions and geographic variability of major conditions causing mortality in Canada. Rates are age-standardized to permit comparison of the relative impact of different conditions in populations with differing age structures. Identifying such geographic variation can help generate hypotheses about explanations for these differences and identify areas for further investigation. It can also contribute to an estimate of the scope for prevention and provide realistic and achievable targets for programs and policies intended to reduce disease burden, in that the lowest rate seen for each condition is clearly achievable under current Canadian conditions.

Adolescent↗

[Nutrition in the etiopathogenesis of chronic inflammatory bowel diseases].

It is currently held that the pathogenesis of inflammatory bowel disease (IBD) involves a complex interaction of host responses, some immunologic and genetically determined, and external influences including microbial and dietary factors. Nutritional surveys and studies testing stepwise exclusion dietary compounds have suggested that dietary factors might be linked to the occurrence of IBD. Food allergy was suggested early as a possible trigger for the inflammatory response; however, no firm evidence has been gathered over the years to substantiate this possibility. The possibility that patients with Crohn's disease may have an unusual premorbid pattern of dietary intake has also been examined since the early seventies. Several groups of investigators report a high intake of refined sugars (i.e. sucrose), recycled cooking oil, a more frequent consumption of fast foods in patients with Crohn's disease and ulcerative colitis respectively. However, a critical comparison of incidence and prevalence studies published from 1976 until 1994 clearly showed no pre-existing nutritional abnormality that has been identified consistently in patients who develop inflammatory bowel disease.

Adolescent↗

[Orthotopic reconstruction in the female, with Kock's ileal neobladder (updated experience in 34 patients)].

At USC around 90% of female patients undergoing cystectomy have become potential candidates for lower urinary tract reconstruction. There are two important criteria when considering the procedure: the continence mechanism must be preserved (by preserving pudendal innervation) and the cancer surgery should not be compromised by the reconstructive procedure. The reconstruction has a similar appearance and function to the original bladder and does away with the need for a cutaneous stoma, providing a normal micturition pattern and improving the patient's quality of life and self-image. Excellent results have so far been obtained with 34 patients, 85% of whom have achieved continence and the ability to void to conclusion.

Adult↗

Requirement of distal and proximal promoter sequences for chromatin organization of the osteocalcin gene in bone-derived cells.

The osteocalcin (OC) gene encodes a 10 Kda bone-specific protein which is expressed with the onset of mineralization during the differentiation of normal diploid osteoblasts. We have previously reported that transcriptional activation of this gene is accompanied by the presence of two DNase I hypersensitive sites, both located in the promoter region spanning key basal (proximal site, -170 to -70) and steroid-dependent enhancer (distal site, -600 to -400) elements. Here, we have examined stably transfected ROS 17/2.8 cell lines carrying OC promoter-reporter transgenes which contain a series of 5'-deletions and determined the effects of these truncations on the chromatin organization. It has been found that: (1) DNase I hypersensitivity at -600 is not a requirement for vitamin D-dependent transcriptional upregulation; (2) basal transcriptional activity and proximal nuclease hypersensitivity depend exclusively on protein-DNA interactions occurring within the proximal promoter region, and (3) within the chromatin context, the proximal 100 bp promoter fragment, containing essential elements such as the OC box (-99 to -76) and TATA box (-44 to -31), is insufficient to support formation of the proximal nuclease hypersensitive site and transcriptional activity.

Animals↗

Changes in chromatin structure support constitutive and developmentally regulated transcription of the bone-specific osteocalcin gene in osteoblastic cells.

Transcription of the osteocalcin gene, which encodes a 10 kDa bone-specific protein, is controlled by modularly organized basal regulatory sequences and hormone-responsive enhancer elements. We have previously shown that in the ROS 17/2.8 rat osteosarcoma cell line, which continuously expresses the osteocalcin gene, key regulatory elements reside in two DNase I hypersensitive sites that are fucntionally correlated with transcriptional activity. We now report that a specific nucleosomal organization supports this constitutive expression in ROS 17/2.8 cells, and that chromatin remodeling directly correlates with the developmentally regulated transcriptional activation of the osteocalcin gene during differentiation of normal diploid rat osteoblasts. By combining DNase I, micrococcal nuclease, and specific restriction endonuclease digestion analysis, we observed that the presence of DNAse I hypersensitive sites (-170 to -70 and -600 to -400) and a selective nucleosome positioning over the OC gene promoter are directly associated with developmental stage-specific transcriptional activation in bone-derived cells.

Animals↗

Trigger points and tender points: one and the same? Does injection treatment help?

Trigger points are defined as areas of muscle that are painful to palpation and are characterized by the presence of taut bands and the generation of a referral pattern of pain. Tender points are areas of tenderness occurring in muscle, muscle-tendon junction, bursa, or fat pad. When tender points occur in a widespread manner, they are usually considered characteristic of fibromyalgia. Trigger points, which typically occur in a more restricted regional pattern, are indicative of myofascial pain syndrome. In some patients the two phenomena may coexists, and overlap syndromes can occur. Although experienced examiners can generally identify the same tender points, interrater reliability of trigger points has been low in most studies. There is continued controversy regarding the defining characteristics and homogeneity of myofascial pain because of the variability of the examination findings. In appropriately selected patients, it appears that myofascial trigger point injections can be helpful in decreasing pain and improving range of motion in conjunction with a comprehensive exercise and rehabilitation program.

Fibromyalgia↗

Development of pericyte-like cells during angiogenesis in quail chick chimeras as detected by combined Feulgen reaction and immunohistochemistry.

Perivascular fibroblasts have been proposed as possible precursor cells for microvascular pericytes. To investigate the development of pericytes during angiogenesis we examined interspecific grafts between chick and quail embryos. Limb buds of three-day old quail embryos were transferred to the chorioallantoic membrane (CAM) of ten to fourteen day-old chick embryos. Six days after grafting, the limb buds were explanted and histologically examined by combined Feulgen reaction and immunohistochemistry using an antibody to quail endothelial and hemopoietic cells (QH-1). Limb buds were found to be vascularized by a network of capillaries which were partially derived from sprouts of the chick CAM microvasculature. Numerous hybrid capillaries were detected, consisting of host endothelial cells (chick) and graft pericytes (quail). These results provide further support for the idea that microvascular pericytes can evolve from perivascular fibroblasts.

Allantois↗

Induction of glutathione-S-transferase-pi by short-chain fatty acids in the intestinal cell line Caco-2.

Glutathione S-transferases (GSTs) are a multigene family of detoxification and metabolizing enzymes that have been linked with the susceptibility of tissues to environmental carcinogens. In addition to their role as the main energy source in the colonic mucosa, short-chain fatty acids (SCFAs) have been found to act as potent antiproliferative and differentiating agents in various cancer cell lines. The objective of this study was to evaluate the effects of SCFAs on the induction of GSTpi in the intestine as a possible new anticarcinogenic mechanism of SCFAs. Studies were performed in Caco-2 cells, a cell line resembling functionally normal enterocytes. Cells, cultured in DMEM supplemented with 10% fetal calf serum, were studied from day 0 dpc (days post confluence) until 21 dpc and culture. SCFAs (acetate, propionate, butyrate) were added to give a final concentration of 5 mmol L(-1). At 0, 3, 6, 9, 15, and 21 dpc, protein, lactate dehydrogenase (LDH), alkaline phosphatase (AP) and GSTpi were measured. Butyrate supplementation significantly (P < or = 0.01) increased GSTpi levels compared with controls in a concentration-dependent manner. The effect was detectable within 3 dpc with a maximum at 15 dpc. In contrast to butyrate, the other SCFAs tested had no (acetate) or little effect (propionate). In conclusion, the data suggest that the anticancer effect of butyrate in part may be based on the induction of GSTpi activity, resulting in an enhanced detoxification capacity of the gut.

Butyrates↗

Antinociceptive response to nitrous oxide is mediated by supraspinal opiate and spinal alpha 2 adrenergic receptors in the rat.

BACKGROUND: Despite nearly 150 years of clinical use, the mechanism(s) of action of nitrous oxide (N2O) remains in doubt. In some but not all studies the analgesic properties of N2O can be attenuated by opiate receptor antagonists. The purported mechanism for the opiate antagonistic effect relates to the finding that N2O increases supraspinal levels of endogenous opiates, although this finding has been disputed. Based on the observations that (1) N2O promotes the release of catecholamines, including the endogenous alpha 2 adrenergic agonist norepinephrine, and (2) that descending noradrenergic inhibitory pathways are activated by opioid analgesics, this study sought to determine whether alpha 2 adrenergic receptors are involved in the antinociceptive action of nitrous oxide. METHODS: Institutional approval was obtained for the study. Rats breathed 70% N2O and 30% O2 in an enclosed chamber. After a 30-min exposure, significant antinociception was indicated by an increase in the latency response to a noxious stimulus (tail-flick latency). The tail-flick latency was tested in rats exposed to 70% N2O after either systemic or regional (intrathecal or intracerebroventricular) injections with either competitive (atipamezole; yohimbine) or noncompetitive (N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline) alpha 2 adrenoceptor antagonists, or the opiate receptor antagonist naloxone. RESULTS: When administered systemically, both the opiate (naloxone) and alpha 2 adrenoceptor antagonists (atipamezole, yohimbine, and N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline) blocked the enhanced tail-flick latency response to N2O-Naloxone administered intracerebroventricularly, but not intrathecally, blocked the enhanced tail-flick latency response to N2O. Conversely, atipamezole administered intrathecally, but not intracerebroventricularly, blocked the enhanced tail-flick latency response to N2O. CONCLUSIONS: These data suggest that both supraspinal opiate and spinal alpha 2 adrenoceptors play a mediating role in the antinociceptive response to N2O in rats. A possible mechanism may involve a descending inhibitory noradrenergic pathway that may be activated by opiate receptors in the periaqueductal gray region of the brain stem in the rat after exposure to N2O.

Adrenergic alpha-Antagonists↗

Dosimetric verification of intensity-modulated fields.

The optimization of intensity distributions and the delivery of intensity-modulated treatments with dynamic multi-leaf collimators (MLC) offer important improvements to three-dimensional conformal radiotherapy. In this study, a nine-beam intensity-modulated prostate plan was generated using the inverse radiotherapy technique. The resulting fluence profiles were converted into dynamic MLC leaf motions as functions of monitor units. The leaf motion pattern data were then transferred to the MLC control computer and were used to guide the motions of the leaves during irradiation. To verify that the dose distribution predicted by the optimization and planning systems was actually delivered, a homogeneous polystyrene phantom was irradiated with each of the nine intensity-modulated beams incident normally on the phantom. For each exposure, a radiographic film was placed normal to the beam in the phantom to record the deposited dose. The films were calibrated and scanned to generate 2-D isodose distributions. The dose was also calculated by convolving the incident fluence pattern with pencil beams. The measured and calculated dose distributions were compared and found to have discrepancies in excess of 5% of the central axis dose. The source of discrepancies was suspected to be the rounded edges of the leaves and the scattered radiation from the various components of the collimation system. After approximate corrections were made for these effects, the agreement between the two dose distributions was within 2%. We also studied the impact of the "tongue-and-groove" effect on dynamic MLC treatments and showed that it is possible to render this effect inconsequential by appropriately synchronizing leaf motions. This study also demonstrated that accurate and rapid delivery of realistic intensity-modulated plans is feasible using a dynamic multi-leaf collimator.

Biophysical Phenomena↗

Intensity modulation optimization, lateral transport of radiation, and margins.

Intensity modulation provides greatly increased control, leading to superior dose distributions with a potential for improved clinical outcome. It also allows us to compensate for deviations from the expected patterns in dose distributions caused by the lateral transport of radiation. This is important not only to produce more homogeneous dose distributions in the target volume but also, more importantly, to allow a reduction in the margins for the penumbra and a corresponding reduction in the volume of normal tissue irradiated. Potentially, this would permit escalation of doses to higher levels and further improve local control for the same or lower normal tissue complications. The intensity-modulated treatment design process, regardless of the specific method used, involves the tracing of rays from the source of radiation through the target volume. Intensities of rays are adjusted iteratively in an attempt to produce a desired homogeneous dose within the target volume, while at the same time striving to maintain normal tissue exposure within the limits of tolerance. If the lateral transport of scattered radiation is ignored, as is commonly done because of the complexities of incorporating it, the resulting dose distribution within the target volume may be considerably different from the anticipated pattern. This would be particularly true if there are high gradients in fluence patterns within the field to shield a normal anatomic structure. Similarly, the lateral transport of radiation would lead to a dose deficit just inside the boundary of the planning target volume (PTV) and a dose excess just outside it. The conventional remedy to make up for the loss of dose near the boundaries, thereby ensuring complete coverage of the target volume, would be to employ a margin for the "penumbra." We demonstrate that, with intensity modulation, we have an important new tool to improve target coverage, namely an appropriate increase in fluence just inside the boundary. Most suitably, a combination of increased fluence and a smaller than conventional margin should be employed. We have used an iterative scheme to compensate for lateral transport in the intensity modulation optimization process. In each iteration, the intensity distribution is first designed ignoring lateral transport. At the end of each iteration, the dose distribution is calculated using a pencil beam convolution method, thereby incorporating lateral transport and revealing the deviations from the anticipated dose distribution caused by lateral transport. In the next iteration, ray intensities are further adjusted to rectify the deviations. In general, only a few iterations are needed to adequately account for the lateral transport of radiation. We have applied this method to intensity-modulated prostate treatment plans and demonstrate that this methodology allows the use of smaller margins, improves target dose homogeneity, and provides greater protection for normal tissues. We examine the variation of the magnitude of the gain from one patient to another. The methodology described in this paper has been introduced into routine clinical use.

Biophysical Phenomena↗

Inactivation of the very strong HCMV immediate early promoter by DNA CpG methylation in vitro.

The influence of DNA methylation in vitro on the activity of the very strong human cytomegalovirus (HCMV) major immediate early (IE) modulator/enhancer/promoter region was investigated by transient transfection experiments of premonocytic HL-60 cells. While sequence-specific methylation of the major IE enhancer and/or modulator with the cytosine methyl-transferases FnuDII, HhaI and HaeIII had no significant effect, the promoter activity was completely repressed by methylation of the cytosine in 5'-CpG sites with the Spiroplasma methyltransferase SssI. Addition of TNF-alpha or PMA which are strong stimulators of HCMV major IE enhancer/promoter activity in premonocytic HL-60 cells had no effect on repression. Inactivation of the IE enhancer/promoter via methylation by M.SssI could be partially alleviated by co-transfection with an excess of untranscribable highly methylated DNA. These results indicate that a methyl-CpG binding factor is involved as mediator in the inhibitory effect of HCMV enhancer/promoter methylation. Taken together, the HCMV major IE enhancer/ promoter has been shown to be susceptible to transcriptional inactivation by methylation of the cytosines in CpG dinucleotides, a process that is proposed to play a modulatory role in viral latency.

Antigens, Viral↗

Immunoreactive elastase I: clinical evaluation of a new noninvasive test of pancreatic function.

We have evaluated the diagnostic value of the fecal elastase test in comparison with the secretin-pancreozymin test in the diagnosis of exocrine pancreatic insufficiency. Pancreatic elastase was measured immunologically. Immunoreactive elastase activity in spot stools from controls ranged from 136 to 4440 microgram/g; 95% of all values were within 175 to 1500 microgram/g. The elastase assay CVs ranged from 3.3% to 6.3% (intraassay) and from 4.1% to 10.2% (interassay). The output of elastase correlated well with those of amylase, lipase, and trypsin, yielding respective correlation coefficients of 0.83, 0.82, and 0.84 in controls and 0.86, 0.91, and 0.91 in patients with impaired pancreatic function. In contrast to fecal chymotrypsin, the test results were unaffected by pancreatic enzyme replacement therapy. These results indicate that fecal immunoreactive elastase may be recommended as a new, noninvasive tubeless test of pancreatic function.

Adolescent↗

Quantification of fecal carbohydrates by near-infrared reflectance analysis.

Established methods for quantitative analysis of fecal carbohydrates (CHO) are time consuming, require unpopular sample handling, and are therefore rarely performed. The aim of this study was to evaluate the efficiency, validity, and practicability of near-infrared reflectance analysis (NIRA), compared with standard methods for measurement of fecal CHO. Excretion of fecal CHO was cross- validated spectrophotometrically with the anthrone method. Fecal CHO concentrations ranged form 2.7 to 24.5 g/kg wet weight. Methods comparison showed linear regression over the entire range of diagnostic relevance with a correlation coefficient of 0.869 (S(y/x) +/- 0.31). Repeated measurements from the same stool collections obviated the need for homogenization. These results indicate that NIRA may be a new, reliable, and accurate test in the diagnosis of CHO malabsorption.

Adolescent↗