PubMed Health⌕ Search

Biomedical subjects

R Stein

Publications and source records attributed to R Stein.

At least 19 recordsLinked to original sources
PubMed2006

The tumor suppressor neurofibromin confers sensitivity to apoptosis by Ras-dependent and Ras-independent pathways.

Neurofibromatosis type 1 (NF1) is characterized by a high incidence of benign and malignant tumors attributed to loss of function of Nf1, which encodes neurofibromin, a tumor suppressor with Ras-GAP activity. Neurofibromin deficiency typically causes chronic activation of Ras, considered the major contributor to manifestation of NF1. Resistance to radio- and chemotherapy are typical of NF1-associated tumors, but the underlying mechanism is unknown. Here, we investigated interrelationships between neurofibromin expression, Ras activity, and sensitivity to apoptosis. Neurofibromin-deficient mouse embryonic fibroblasts (MEFs) and human NF1 tumor cells were more resistant than neurofibromin-expressing cells to apoptosis. Moreover, Nf1(-/-), Nf1(+/-), and Nf1(+/+) MEFs exhibited gene-dosage-related resistance to apoptosis. Resistance of the Nf1-deficient cells was mediated by two survival pathways: a Ras-dependent pathway, and a Ras-independent pathway promoted by the lack of an NF1-GRD-independent proapoptotic action of neurofibromin. Therefore, besides its Ras-dependent growth inhibition, neurofibromin can exert tumor suppression via a proapoptotic effect.

Animals↗
PubMed2006

A 3-year prospective study of the effects of adjuvant treatments on cognition in women with early stage breast cancer.

The neuropsychological performance of 85 women with early stage breast cancer scheduled for chemotherapy, 43 women scheduled for endocrine therapy and/or radiotherapy and 49 healthy control subjects was assessed at baseline (T1), postchemotherapy (or 6 months) (T2) and at 18 months (T3). Repeated measures analysis found no significant interactions or main effect of group after controlling for age and intelligence. Using a calculation to examine performance at an individual level, reliable decline on multiple tasks was seen in 20% of chemotherapy patients, 26% of nonchemotherapy patients and 18% of controls at T2 (18%, 14 and 11%, respectively, at T3). Patients who had experienced a treatment-induced menopause were more likely to show reliable decline on multiple measures at T2 (OR=2.6, 95% confidence interval (CI) 0.823-8.266 P=0.086). Psychological distress, quality of life measures and self-reported cognitive failures did not impact on objective tests of cognitive function, but were significantly associated with each other. The results show that a few women experienced objective measurable change in their concentration and memory following standard adjuvant therapy, but the majority were either unaffected or even improve over time.

Adult↗
PubMed2006

[Hypospadias].

Explore the source record for details and available documents.

Child↗
PubMed2006

Theoretical models in dentistry.

For the exchange between science and practice, a language that is as precise as possible is also required in dentisty. This language is necessarily based on our ideas about the relationships in reality. Since standardization is unavoidable, various methods have been developed in informatics as to how these models can be represented and made more precise. On this basis, it is possible to neutrally discuss the situations in which a given form of treatment is expedient or not. A step-by-step approach to standardization of dental language with the aid of meta models is shown by reference to examples. The medrapid.info service is presented as on approach to making medical and dental language more precise.

Computer Systems↗
PubMed2005

Aluminium in Alzheimer's disease: are we still at a crossroad?

Aluminium, an environmentally abundant non-redox trivalent cation has long been implicated in the pathogenesis of Alzheimer's disease (AD). However, the definite mechanism of aluminium toxicity in AD is not known. Evidence suggests that trace metal homeostasis plays a crucial role in the normal functioning of the brain, and any disturbance in it can exacerbate events associated with AD. The present paper reviews the scientific literature linking aluminium with AD. The focus is on aluminium levels in brain, region-specific and subcellular distribution, its relation to neurofibrillary tangles, amyloid beta, and other metals. A detailed mechanism of the role of aluminium in oxidative stress and cell death is highlighted. The importance of complex speciation chemistry of aluminium in relation to biology has been emphasized. The debatable role of aluminium in AD and the cross-talk between aluminium and genetic susceptibility are also discussed. Finally, it is concluded based on extensive literature that the neurotoxic effects of aluminium are beyond any doubt, and aluminium as a factor in AD cannot be discarded. However, whether aluminium is a sole factor in AD and whether it is a factor in all AD cases still needs to be understood.

Aluminum↗
PubMed2005

Bak but not Bax is essential for Bcl-xS-induced apoptosis.

Bcl-x(S), a proapoptotic member of the Bcl-2 protein family, is localized in the mitochondria and induces apoptosis in a caspase- and BH3-dependent manner by a mechanism involving cytochrome c release. The way in which Bcl-x(S) induces caspase activation and cytochrome c release, as well as the relationship between Bcl-x(S) and other proapoptotic members of the Bcl-2 family, is not known. Here we used embryonic fibroblasts derived from mice deficient in the multidomain proapoptotic members of the Bcl-2 family (Bax and Bak) and the apoptotic components of the apoptosome (Apaf-1 and caspase-9) to unravel the cascade of events by which Bcl-x(S) promotes apoptosis. Our results show that Bak but not Bax is essential for Bcl-x(S)-induced apoptosis. Bcl-x(S) induced activation of Bak, which in turn promoted apoptosis by apoptosome-dependent and -independent pathways. These findings provide the first evidence that a proapoptotic Bcl-2 family protein induces apoptosis exclusively via Bak.

Animals↗
PubMed2005

[Pericardial empyema due to oropharyngeal infection -- a rare entity].

Both the descending necrotizing mediastinitis (DNM) and the pericardial empyema are rare but life threatening situations, in which rapid aggressive surgical approach is important for the outcome. A 37-year-old man presented with reduced general health and new establishment of thoracal pain after an infection in the oropharyngeal region. The dissemination of the infection into the mediastinum (mediastinitis) diagnosed by clinic and radiography required surgical intervention. A pericardial empyema was detected intraoperatively. The patient was discharged home on the 14 (th) hospital day.

Adult↗
PubMed2004

[Children and youths with neurogenic disturbances of bladder function. Bladder augmentation, substitution and the diversion of urine].

After the failure of conservative treatment in patients with neurogenic bladders, urinary diversion is a viable compromise between the urologist's concerns and the patient's desire, as the upper urinary tract can be protected in the long-term and high continence rates can be provided. This can be achieved with an acceptable complication rate. Our indications for orthotopic bladder augmentation or substitution involve patients with a good orthopedic condition and mobility, who find it easy to perform CISC through the urethra. A continent umbilical stoma offers a good alternative in obese, immobile or wheelchair bound patients. The serous lined extramural tunnel technique has proven to be superior to submucosal implantation in patients with fibrotic and dilated ureters.

Adolescent↗
PubMed2004

Rhabdomyosarcoma of the bladder, prostate or vagina: the role of surgery.

OBJECTIVE: To retrospectively analyse the outcome of children with rhabdomyosarcoma (RMS) of the bladder, prostate or vagina who were treated with chemotherapy, with or without radical surgery or additional radiotherapy, at our institution since 1968. PATIENTS AND METHODS: From a total of 107 children with RMS seen between 1968 and December 2001, 22 (mean age 5.9, range 0.5-18) had RMS of bladder/prostate or vagina. Twenty of the patients received primary polychemotherapy (vincristine, actinomycin D, cyclophosphamide, adriamycin, and more recently including etoposide and ifosfamide), two had primary surgery and seven had additional radiotherapy. Fourteen patients had radical cystoprostatectomy, with continent cutaneous urinary diversion with an ileocaecal pouch in seven, in one each a transverse colonic pouch, orthotopic ileocaecal bladder substitution, a rectal reservoir and rectosigmoid pouch and a colonic conduit diversion in two patients. RESULTS: After a mean (range) follow-up of 8.6 (1.0-26) years, 17 patients had no evidence of disease. Five patients presenting initially with advanced tumour stages died from progressive RMS. Two patients with a continent urinary diversion required ureteric reimplantation for stenosis. In two patients severe bladder contraction after radiotherapy required bladder augmentation. CONCLUSION: Primary chemotherapy followed by radical surgery of RMS of the prostate and/or bladder allows complete tumour resection in most cases, and yields excellent cure rates.

Adolescent↗
PubMed2003

Heavy metals in aerosols over the seas of the Russian Arctic.

A review of the data on heavy metals in aerosols over the seas of the Russian Arctic is presented. Results of heavy metal studies in aerosols obtained during 11 research expeditions in summer/autumn period from 1991 to 2000, and at Severnaya Zemlya and Wrangel Island in spring, in 1985-1989 are discussed. Concentrations of most heavy metals in the atmosphere in the marine boundary layer in the Russian Arctic are nearly of the same order as literature data from other Arctic areas. The content of heavy metals in the aerosols over the seas of the Russian Arctic shows an annual variation with maximal concentrations during the winter/spring season. In the summer/autumn period increased concentrations of heavy metals could be explained, in most cases, by natural processes (generation of sea salt aerosols, etc.). In some cases, aerosols from Norilsk and Kola Peninsula were detected. Particular attention was paid to estimation of horizontal and vertical fluxes of atmospheric heavy metals. We estimated annual variations in long-range transport of heavy metals into the Russian Arctic in 1986-1995. In winter and spring, up to 50% of the average air pollutant concentrations in the Russian Arctic are due to the Arctic atmospheric pollution itself. Moreover, the monthly and annual averaged fluxes of six anthropogenic chemical elements (arsenic, nickel, lead, vanadium, zinc and cadmium) onto the surface in the Arctic were estimated, and the values obtained were in reasonable agreement with the literature data available.

Aerosols↗
PubMed2003

Overexpression of wild-type presenilin 2 or its familial Alzheimer's disease-associated mutant does not induce or increase susceptibility to apoptosis in different cell lines.

Programmed cell death, or apoptosis, has been implicated in Alzheimer's disease. Mutations in the presenilin (PS) genes, PS1 and PS2, are a major cause of early-onset familial Alzheimer's disease (FAD). Previous studies have suggested that the PS play a role in apoptosis. However, the mechanisms whereby presenilins affect apoptosis and the relationship of FAD-associated presenilin mutants to the apoptotic effect have not been elucidated. In the present study, in an attempt to further explore the effect of PS2 on apoptosis we examined whether overexpression of wild-type or mutant PS2 can directly induce apoptosis or increase cell susceptibility to apoptosis in various cell lines, such as N2a, CHO, and HEK 293T. Wild-type or mutant PS2 was transiently transfected into these cell lines and the viability of the transfected cells was evaluated by their morphology, DNA fragmentation and condensation, appearance of sub-G(1/0) cells, and caspase activation. We also examined the susceptibility of the PS2-transfected cells to apoptosis induced by the apoptotic inducers staurosporine and H(2)O(2). Our results showed that overexpression of either wild type or mutant PS2 in these cell lines did not directly induce apoptosis or increase the susceptibility to apoptosis induced by staurosporine or H(2)O(2). Taken together, these results suggest that overexpression of PS2 does not cause pro-apoptotic effects, at least not in the cellular systems and conditions employed in this study, and therefore it seems unlikely that apoptosis plays a prominent role in the neuropathological effects of PS2 in Alzheimer's disease.

Alzheimer Disease↗
PubMed2002

Long-term followup of 158 young adults surgically treated for vesicoureteral reflux in childhood: the ongoing risk of urinary tract infections.

PURPOSE: We recorded urinary tract infections in the long term after surgical reflux correction. MATERIALS AND METHODS: A total of 158 of 189 patients (160 females and 29 males) who were followed in 1985, an average of 10.8 years after reflux surgery were contacted again in 1995. At that time median patient age was 26 years (range 15.7 to 38.8) and the average period of observation was 20.3 years (range 13.4 to 26). RESULTS: In 82% of the patients febrile and in 18% afebrile symptomatic urinary tract infections had developed preoperatively. In the first 10-year period after operation 46% of patients continued to have symptomatic urinary tract infections compared with 52% in the second 10-year interval. In the 2 periods the incidence of febrile urinary tract infection was about 17%. In the whole postoperative observation period symptomatic urinary tract infections developed in 66% of all patients, including 74% of female patients. Symptomatic urinary tract infections were observed during 8 of 46 pregnancies (17%). CONCLUSIONS: After successful surgical reflux correction susceptibility to urinary tract infection continues for a number of years in many girls and women. However, postoperatively urinary tract infections are primarily afebrile.

Adolescent↗