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Biomedical subjects

A Stein

Publications and source records attributed to A Stein.

At least 19 recordsLinked to original sources

A proteomic analysis reveals the loss of expression of the cell death regulatory gene GRIM-19 in human renal cell carcinomas.

Gene associated with retinoid interferon-induced mortality (GRIM)-19, an inhibitor of transcription factor STAT3, was originally identified as a critical regulatory protein in a genetic screen that was designed to identify the gene products necessary for Interferon (IFN)-beta- and retinoic acid-induced cell death. Over expression of GRIM-19 activates cell death. Conversely, inactivation of its expression promotes cell growth. STAT3 is a transcription factor that regulates gene expression in response to multiple extra cellular growth factors. In contrast to its normal feedback inhibition, a constitutive activation of STAT3 has been documented in several tumors. Although many STAT3-inhibitors are described, their relevance to human cancer is unclear. In an attempt to define the molecular alterations associated with human renal cell carcinoma (RCC) using mass spectrometry, we have discovered that expression of GRIM-19 is lost or severely depressed in a number of primary RCC and in some urinogenital tumors. Using an RCC cell line, we show that down regulation of GRIM-19 promotes tumor growth via an augmentation of STAT3-dependent gene expression. These studies for the first time show a tumor-suppressor like activity of GRIM-19.

Apoptosis Regulatory Proteins↗

[Pancreatic panniculitis with neuroendocrine pancreatic carcinoma].

Pancreatic panniculitis is a rare complication occurring in 0.3-3% of patients with pancreatic disease. Clinical features include erythematous painful subcutaneous nodules usually on the lower leg and foot. A 72-year-old man was diagnosed in 2002 with a neuroendocrine carcinoma of the head of the pancreas. In 2003 following surgery and radiation therapy, he developed liver metastases and painful nodules on his legs. Lipase was found to be markedly elevated; amylase and alpha1-antitrypsin were in the normal range. Histopathologic examination of a nodule showed subcutaneous fat necrosis with ghost cells surrounded by an acute inflammatory infiltrate. The pathogenesis of pancreatic panniculitis is unclear. The pancreatic enzyme lipase may induce lipolysis and fat necrosis with secondary tissue inflammation.

Aged↗

[Therapy of cutaneous metastases of malignant melanoma].

Malignant melanoma represents a particular challenge for dermatologists and oncologists because of its high and increasing incidence and the poor prognosis of patients with thick primary tumors (T3, T4). In advanced stages of melanoma, cutaneous and subcutaneous metastases have a special significance, as they markedly affect the patient and may lead to a limitation in quality of life. While topical therapy is possible, there are only limited clinical studies. The location, number, size and distribution of skin metastases, involvement of internal organs, age and general condition should be considered in assessing therapeutic options. Especially with solitary, easily accessible metastases, surgical excision represents the therapy of choice. Ablation using CO(2) laser is an alternative. With extensive metastases in just one extremity, isolated limb perfusion (ILP) with melphalan is an option, while multiple, smaller metastases can be irradiated. Further, several chemotherapeutic agents and immune modulators can be used topically, peri- and intralesionally.

Antineoplastic Agents, Alkylating↗

Post-partum depression and infant growth in a South African peri-urban settlement.

AIM: To examine the association between maternal post-natal depression and infant growth. BACKGROUND: Infant growth has recently been shown, in two studies from South Asia, to be adversely affected by maternal depression in the early post-partum period. It is uncertain whether a similar association obtains in developing countries outside Asia. METHOD: A sample of 147 mother-infant dyads was recruited from a peri-urban settlement outside Cape Town and seen at 2 and 18 months post partum. RESULTS: No clear effect of post-partum depression on infant growth was found. Although maternal depression at 2 months was found to be associated with lower infant weight at 18 months, when birthweight was considered this effect disappeared. CONCLUSIONS: Possible explanations for the non-replication of the South Asian findings are considered.

Adult↗

Pseudosyndactyly and musculoskeletal contractures in inherited epidermolysis bullosa: experience of the National Epidermolysis Bullosa Registry, 1986-2002.

Mitten deformities of the hands and feet occur in nearly every patient with the most severe subtype (Hallopeau-Siemens) of recessive dystrophic epidermolysis bullosa, and in at least 40-50% of all other recessive dystrophic epidermolysis bullosa patients. Smaller numbers of patients with dominant dystrophic, junctional, and simplex types of epidermolysis bullosa are also at risk of this complication. Surgical intervention is commonly performed to correct these deformities, but recurrence and the need for repeated surgery are common. Higher numbers of epidermolysis bullosa patients also develop musculoskeletal contractures in other anatomic sites, further impairing overall function. Lifetable analyses not only better project the cumulative risk of mitten deformities and other contractures but also emphasize the need for early surveillance and intervention, since both of these musculoskeletal complications may occur within the first year of life.

Adolescent↗

Low-level laser irradiation promotes proliferation and differentiation of human osteoblasts in vitro.

OBJECTIVES: The aim of the present study was to investigate the effect of low-level laser irradiation on proliferation and differentiation of a human osteoblast cell line. BACKGROUND DATA: It was previously found that low-level laser therapy (LLLT) enhances bone repair in experimental models. MATERIALS AND METHODS: Cultured osteoblast cells were irradiated using He-Ne laser irradiation (632 nm; 10 mW power output). On the second and third day after seeding the osteoblasts were exposed to laser irradiation. The effect of irradiation on osteoblast proliferation was quantified by cell count and colorimetric MTT (dimethylthiazol tetrazolium bromide) assay 24 and 48 h after second irradiation. RESULTS: A significant 31-58% increase in cell survival (MTT assay) and higher cell count in the once-irradiated as compared to nonirradiated cells was monitored. Differentiation and maturation of the cells was followed by osteogenic markers: alkaline phosphatase (ALP), osteopontin (OP), and bone sialoprotein (BSP). A two-fold enhancement of ALP activity and expression of OP and BSP was much higher in the irradiated cells as compared to non-irradiated osteoblasts. CONCLUSION: We conclude that LLLT promotes proliferation and maturation of human osteoblasts in vitro. These results may have clinical implications.

Alkaline Phosphatase↗

The effects of maternal depression and parental conflict on children's peer play.

BACKGROUND: Little is known about the relative effects of exposure to postnatal depression and parental conflict on the social functioning of school-aged children. This is, in part, because of a lack of specificity in the measurement of child and parental behaviour and a reliance on children's reports of their hypothetical responses to conflict in play. METHODS: In the course of a prospective longitudinal study of children of postnatally depressed and well women, 5-year-old children were videotaped at home with a friend in a naturalistic dressing-up play setting. As well as examining possible associations between the occurrence of postnatal depression and the quality of the children's interactions, we investigated the influence of parental conflict and co-operation, and the continuity of maternal depression. The quality of the current mother-child relationship was considered as a possible mediating factor. RESULTS: Exposure to postnatal depression was associated with increased likelihood, among boys, of displaying physical aggression in play with their friend. However, parental conflict mediated the effects of postnatal depression on active aggression during play, and was also associated with displays of autonomy and intense conflict. While there were no gender effects in terms of the degree or intensity of aggressive behaviours, girls were more likely to express aggression verbally using denigration and gloating whereas boys were more likely to display physical aggression via interpersonal and object struggles. CONCLUSIONS: The study provided evidence for the specificity of effects, with strong links between parental and child peer conflict. These effects appear to arise from direct exposure to parental conflict, rather than indirectly, through mother-child interactions.

Adult↗

Oral and dental aspects of chronic renal failure.

The present article reviews, in detail, the current knowledge of the oral and dental aspects of chronic renal failure (CRF). Worldwide, increasing numbers of persons have CRF; thus, oral health care staffs are increasingly likely to provide care for patients with such disease. Chronic renal failure can give rise to a wide spectrum of oral manifestations, affecting the hard or soft tissues of the mouth. The majority of affected individuals have disease that does not complicate oral health care; nevertheless, the dental management of such individuals does require that the clinician understand the multiple systems that can be affected. The clinician should also consider the adverse side-effects of drug therapy and appropriate prescribing, in view of compromised renal clearance.

Dental Care for Chronically Ill↗

Year-round screening of noncommercial and commercial oysters for the presence of human pathogenic viruses.

Consumption of virus-contaminated shellfish has caused numerous outbreaks of gastroenteritis and hepatitis worldwide. In The Netherlands, oysters are cultured and imported both for consumption and export; therefore, the presence of noroviruses, rotaviruses, astroviruses, hepatitis A viruses, and enteroviruses was determined in 64 commercial and noncommercial oyster samples. Oysters were collected monthly for 13 months from four different harvesting areas in the Oosterschelde Delta. Oyster samples were classified by determining Escherichia coli levels according to the standards set by the Councils Directive (91/ 492/EEC). Two of 36 commercial and 2 of 28 noncommercial oyster samples were B-classified and therefore not ready for consumption. All other oyster samples were A-classified. For the detection of viral RNA, 150 mg of hepatopancreatic tissue was subjected to the Qiagen RNeasy Mini Kit, followed by reverse transcriptase (RT)-PCR and Southern blot hybridization. Enterovirus RNA was detected in 14 of 64 oyster samples, of which 4 were from noncommercial oyster harvesting areas and 10 were from commercial harvesting areas. None of the other human pathogenic viruses were detected. The levels of somatic coliphages and F-specific phages were also determined in all 64 oyster samples, with some samples containing high phage levels (>50 PFU/g of hepatopancreatic tissue), but with most samples containing low phage levels (<50 PFU/g of hepatopancreatic tissue). However, independent of these high or low phage levels, enterovirus RNA could be detected. Thus, commercial oysters can be contaminated with pathogenic viruses, and monitoring only fecal indicators might not sufficiently protect human health.

Animals↗

MAGE-A8 overexpression in transitional cell carcinoma of the bladder: identification of two tumour-associated antigen peptides.

Bladder carcinoma is the fourth most common cancer in men and the eighth most common cancer among women. Our study is aimed to characterise tumour-associated antigen peptides of transitional cell carcinoma of the bladder (TCC). A DNA micro-array-based differential display analysis of 10 000 genes was carried out, and MAGE-A8 gene expression was detected in the tumour, and not in the normal bladder. High occurrence of MAGE-A8 expression was observed in fresh tumour samples (17 out of 23) and TCC lines (four of eight). The MAGE-A8 protein sequence was screened for HLA-A2.1-binding motifs, six potential peptides were synthesised, and peptides binding to HLA-A2.1 were assured. Immunogenicity and antigenicity of the MAGE-A8 peptides were examined in the HHD system, murine class I MHC knockout mice, transgenic for HLA-A2.1. The MAGE-A8 peptide immunogenicity was examined in three modes of vaccination, delivered intranasally with cholera toxin, injected into the tail base with complete Freund's adjuvant (CFA), or presented directly as loaded onto cell surface HLA-A2.1 molecules. Two peptides, 8.1 and 8.3, induce CTL that kills the T24 TCC line in vitro, and prime human lymphocyte response of healthy donors. These results demonstrate the potential use of the MAGE-A8 peptides for specific immunotherapy of TCC.

Animals↗

[CT evaluation of total HIP prosthesis infection].

PURPOSE: To evaluate the ability of CT imaging to detect infectious lesions in total hip prosthesis. PATIENTS AND METHODS: CT was performed in 17 cases of suspected total hip prosthesis infection. Images were reviewed to evaluate for the presence of soft tissue abscess, hip joint effusion or fistula and peri-prosthetic lucency or erosion at bone window setting. The feasibility of CT imaging is assessed with regards to metallic artifacts. RESULTS: Infection was confirmed in 10 hips. A soft tissue abscess was present in 8 of these cases, in association to a joint effusion, presumably septic, in 7 cases. A fistula was identified in 8 cases. A peri-prosthetic lucency was present in 10 cases, 7 of which with infection, and erosions were noted in 4 patients, 2 of which with infection. Metallic artifacts reduced image quality but did not prevent detection of soft tissue abscesses. CONCLUSION: CT is useful for detection of soft tissue abscesses in patients with infected hip prosthesis. CT is useful for surgical planning or follow-up of patients treated conservatively.

Aged↗

Cyclosporine and mycophenolate mofetil prophylaxis with fludarabine and melphalan conditioning for unrelated donor transplantation: a prospective study of 22 patients with hematologic malignancies.

In an attempt to decrease toxicity in high-risk patients undergoing unrelated donor hematopoietic stem cell transplantation (URD HSCT), we tested a combination of cyclosporine (CSP) and mycophenolate mofetil (MMF) as graft-versus-host disease (GVHD) prophylaxis with the reduced-intensity conditioning regimen fludarabine/melphalan (Flu/Mel). A total of 22 adult patients with advanced myeloid (n=15) and lymphoid (n=7) malignancies were treated. All patients received Flu 25 mg/m2 for 5 days and Mel 140 mg/m2, with CSP 3 mg/kg daily and MMF 15 mg/kg three times a day. The median age was 49 years (range 18-66). Durable engraftment was seen in all but one patient with myelofibrosis. The 1-year nonrelapse mortality was 32%, 27% from GVHD. The cumulative incidence of acute GVHD grade 2-4 and 3-4 was 63 and 41%, respectively. With a median follow-up of 18 months, the disease-free survival (DFS) and overall survival (OS) are 55 and 59%, respectively. For patients with AML and MDS (n=14), the DFS and OS is 71%. For patients undergoing a second transplant (n=14), the DFS and OS is 57%. In conclusion, this regimen is associated with acceptable toxicity but high rates of GVHD in high-risk patients undergoing URD HSCT. Encouraging disease control for patients with advanced myeloid malignancies was observed.

Adolescent↗

A method for determining void arrangements in inverse opals.

The periodic arrangement of voids in ceramic materials templated by colloidal crystal arrays (inverse opals) has been analysed by transmission electron microscopy. Individual particles consisting of an approximately spherical array of at least 100 voids were tilted through 90 degrees along a single axis within the transmission electron microscope. The bright-field images of these particles at high-symmetry points, their diffractograms calculated by fast Fourier transforms, and the transmission electron microscope goniometer angles were compared with model face-centred cubic, body-centred cubic, hexagonal close-packed, and simple cubic lattices in real and reciprocal space. The spatial periodicities were calculated for two-dimensional projections. The systematic absences in these diffractograms differed from those found in diffraction patterns from three-dimensional objects. The experimental data matched only the model face-centred cubic lattice, so it was concluded that the packing of the voids (and, thus, the polymer spheres that composed the original colloidal crystals) was face-centred cubic. In face-centred cubic structures, the stacking-fault displacement vector is a/6<211> . No stacking faults were observed when viewing the inverse opal structure along the orthogonal <110>-type directions, eliminating the possibility of a random hexagonally close-packed structure for the particles observed. This technique complements synchrotron X-ray scattering work on colloidal crystals by allowing both real-space and reciprocal-space analysis to be carried out on a smaller cross-sectional area.

Ceramics↗

Is assisted hatching beneficial in patients with recurrent implantation failures?

PURPOSE: To assess the possible role of assisted hatching in patients with recurrent implantation failure during IVF cycles. DESIGN: Prospective randomized study. SETTING: IVF unit of an academic medical center. PATIENTS: Women who underwent IVF after at least three failed IVF-ET attempts. INTERVENTIONS: Patients were prospectively randomized to undergo assisted hatching of their embryos prior to their replacement by mechanical partial zona dissection. RESULTS: The study (assisted hatching) and control groups included 104 and 103 patients, respectively. There were no significant between-group differences in patient age, cause of infertility, mean number of previous IVF trials, number of oocytes retrieved, fertilization rate, or number of embryos transferred. No difference in pregnancy rate was noted on comparison of the whole study group, to the whole control group (21% and 27%, respectively). However, when the results were re-analyzed by age groups, assisted hatching was found to be harmful in the youngest group (< 34 years), significantly decreasing pregnancy rates (15% vs 35%, p < 0.05). CONCLUSION: Repeated implantation failure alone is not an indication for assisted hatching. Although assisted hatching appears to be effective in a selected group of older patients, in younger patients it may further hamper implantation and should be avoided.

Adult↗

Lower esophageal sphincter injection of a biocompatible polymer: accuracy of implantation assessed by esophagectomy.

BACKGROUND: Endoscopic lower esophageal sphincter (LES) implantation of a biocompatible polymer is undergoing clinical trial as an alternative to pharmacologic and laparoscopic treatments for gastroesophageal reflux disease. The safety and efficacy of LES augmentation depend on accurate placement of the implant into the wall of the esophagus. To date, no study has demonstrated the prevalence and location of the intended implant. METHODS: The study group consisted of nine patients with underlying esophageal disease severe enough to warrant esophagectomy. Three or four implants of 1 or 2 cc of Enteryx (a biocompatible ethylene-vinyl alcohol copolymer dissolved in dimethyl sulfoxide with micronized tantalum as a radiopaque marker) were placed at the squamocolumnar junction of each patient via a 4-mm, 23-gauge needle under endoscopic guidance. Fluoroscopy was utilized in all patients to facilitate endoscopic placement. Outcome measures included the prevalence and location of successful implantation into the wall of the esophagus. RESULTS: Thirty of 34 implants (88%) were successfully placed into the wall of the esophagus. The remaining 4 were found lying subserosally or attached to the exterior of the gastroesophageal junction (GEJ). Fluoroscopically, the implants often tended to coalesce, forming arcs or a ring around the GEJ. Histologic examination revealed implantation into the deep submucosa contiguous with the circular muscle and within the muscularis propria in all patients, with implants occasionally extending into the subserosa. There were no untoward reactions identified. CONCLUSIONS: Endoscopically directed implantation of a biocompatible polymer into the esophageal wall can be accomplished with a high degree of accuracy. Injection via a 4-mm needle results in the placement of material along and within the muscular layers of the esophagus.

Biocompatible Materials↗