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Biomedical subjects

A Stark

Publications and source records attributed to A Stark.

At least 37 records · Page 2Linked to original sources
PubMed2000

The mitochondrial permeability transition augments Fas-induced apoptosis in mouse hepatocytes.

Tumor necrosis factor-alpha receptor 1 and Fas recruit overlapping signaling pathways. To clarify the differences between tumor necrosis factor alpha (TNFalpha) and Fas pathways in hepatocyte apoptosis, primary mouse hepatocytes were treated with TNFalpha or an agonist anti-Fas antibody after infection with an adenovirus expressing an IkappaB superrepressor (Ad5IkappaB). Treatment with TNFalpha induced apoptosis in Ad5IkappaB-infected mouse hepatocytes, as we previously reported for rat hepatocytes. Ad5IkappaB plus anti-Fas antibody or actinomycin D plus anti-Fas antibody rapidly induced apoptosis, whereas anti-Fas antibody alone produced little cytotoxicity. The proteasome inhibitor (MG-132) and a dominant-negative mutant of nuclear factor-kappaB-inducing kinase also promoted TNFalpha- and Fas-mediated apoptosis. Expression of either crmA or a dominant-negative mutant of the Fas-associated death domain protein prevented TNFalpha- and Fas-mediated apoptosis. In addition, the caspase inhibitors, DEVD-cho and IETD-fmk, inhibited TNFalpha- and Fas-mediated apoptosis. In Ad5IkappaB-infected hepatocytes, caspases-3 and -8 were activated within 2 h after treatment with anti-Fas antibody or within 6 h after TNFalpha treatment. Confocal microscopy demonstrated onset of the mitochondrial permeability transition (MPT) and mitochondrial depolarization by 2-3 h after anti-Fas antibody treatment and 8-10 h after TNFalpha treatment, followed by cytochrome c release. The combination of the MPT inhibitors, cyclosporin A, and trifluoperazine, protected Ad5IkappaB-infected hepatocytes from TNFalpha-mediated apoptosis. After anti-Fas antibody, cyclosporin A and trifluoperazine decreased cytochrome c release but did not prevent caspase-3 activation and cell-death. In conclusion, nuclear factor-kappaB activation protects mouse hepatocytes against both TNFalpha- and Fas-mediated apoptosis. TNFalpha and Fas recruit similar but nonidentical, pathways signaling apoptosis. The MPT is obligatory for TNFalpha-induced apoptosis. In Fas-mediated apoptosis, the MPT accelerates the apoptogenic events but is not obligatory for them.

Animals↗
PubMed2000

The Wagner revision prosthesis consistently restores femoral bone structure.

The short-term results are reported for 43 hip revision operations with the long-stemmed Wagner prosthesis. The patients were followed-up for an average of 25 months. The Charnley scores were; pain 5.2, movement 4.0 and walking 4.0. All patients except one showed abundant new bone formation. The stem subsided more than 20 mm in 5 patients and in 22 the subsidence was less than 5 mm. The major complication was dislocation, which occurred in 9 patients; 8 of these were reoperated and from then on remained stable.

Aged↗
PubMed2000

Synovial fluid from loose hip arthroplasties inhibits human osteoblasts.

Aseptic loosening of prosthetic components in patients who have undergone total hip arthroplasty is a major clinical problem. Earlier studies on this topic have focused mainly on different aspects of bone resorption. The current study investigated the influence of synovial fluid from patients who underwent revision surgery because of aseptic loosening and synovial fluid from patients with osteoarthritis on the proliferation of primary cultures of human osteoblasts. Incubation of cells with 10% synovial fluid from patients who had revision surgery significantly inhibited [3H]thymidine incorporation into deoxyribonucleic acid in human osteoblasts compared with control conditions, whereas 10% synovial fluid from patients with osteoarthritis had a significant stimulatory effect. These findings correlate well with clinical features seen in these diseases, such as increased net bone resorption around the prosthesis in patients with loosening, and increased periarticular bone formation in patients with osteoarthritis.

Aged↗
PubMed2000

Hearing conservation for farmers: source apportionment of occupational and environmental factors contributing to hearing loss.

Those who work on farms continue to have a strikingly high prevalence of hearing loss, despite efforts to promote hearing conservation in agriculture. To develop improved hearing conservation programs, we performed a source apportionment analysis for hearing loss in a large, multiphasic health survey, the New York Farm Family Health and Hazard Survey. We used information from audiometric, otoscopic, and tympanometric examinations; detailed general health and farm exposure interviews; and a second interview that focused on additional potential determinants of hearing loss. Hearing loss on audiometry was significantly associated with increased age, male gender, education through high school or less, lifetime years of hunting with guns, lifetime years of use of a grain dryer, and a history of spraying crops during the previous year. Hearing conservation programs for farmers should thus be directed toward reduction in noise exposure, both from occupational and non-occupational sources. Additional study is needed to evaluate the association seen between crop spraying and hearing loss.

Adult↗
PubMed2000

HER-2/neu amplification in benign breast disease and the risk of subsequent breast cancer.

PURPOSE: The purpose of this study was to determine whether the presence of HER-2/neu gene amplification and/or overexpression in benign breast disease was associated with an increased risk of subsequent breast cancer. PATIENTS AND METHODS: We conducted a nested case-control study of a cohort of women who were diagnosed with benign breast disease at the Mayo Clinic and who were subsequently observed for the development of breast cancer. Patients who developed breast cancer formed the case group, and a matched sample from the remaining cohort served as controls. Benign tissue samples from 137 cases and 156 controls and malignant tissues from 99 cases provided DNA or tissue for evaluation of HER-2/neu amplification and protein overexpression. RESULTS: Among the controls, seven benign tissues (4.5%) demonstrated low-level HER-2/neu amplification, whereas 13 benign (9.5%) and 18 malignant (18%) tissue specimens from cases exhibited amplification. HER-2/neu amplification in benign breast biopsies was associated with an increased risk of breast cancer (odds ratio ¿OR = 2.2; 95% confidence interval ¿CI, 0.9 to 5.8); this association approached statistical significance. The risks for breast cancer associated with benign breast histopathologic diagnoses were OR = 1.1 (95% CI, 0.6 to 1.9) for lesions exhibiting proliferation without atypia and OR = 1.5 (95% CI, 0.4 to 5.6) for the diagnosis of atypical ductal hyperplasia. For women having both HER-2/neu amplification and a proliferative histopathologic diagnosis (either typical or atypical), the risk of breast cancer was more than seven-fold (OR = 7.2; 95% CI, 0.9 to 60.8). Overexpression of the HER-2/neu protein product, defined as membrane staining in 10% or more of epithelial cells, was found in 30% of the breast tumors but was not detected in any of the benign breast tissues. Case patients who had HER-2/neu gene amplification in their malignant tumor were more likely to have had HER-2/neu amplification in their prior benign biopsy (P =.06, Fisher's exact test). CONCLUSION: Women with benign breast biopsies demonstrating both HER-2/neu amplification and a proliferative histopathologic diagnosis may be at substantially increased risk for subsequent breast cancer.

Adult↗
PubMed2000

Ultra-low wear rates for rigid-on-rigid bearings in total hip replacements.

With the increased clinical interest in metal-on-metal and ceramic-on-ceramic total-hip replacements (THRs), the objective of this hip simulator study was to identify the relative wear ranking of three bearing systems, namely CoCr-polyethylene (M-PE), CoCr-CoCr (M-M) and ceramic-on-ceramic (C-C). Volumetric wear rates were used as the method of comparison. The seven THR groupings included one M-PE study, two M-M studies and four C-C studies. Special emphasis was given to defining the 'run-in' phase of accelerated wear that rigid-on-rigid bearings generally exhibit. The hypothesis was that characterization of the run-in and steady state wear phases would clarify not only the tribological performance in vitro but also help correlate these in vitro wear rates with the 'average' wear rates measured on retrieved implants. The implant systems were studied on multichannel hip simulators using the Paul gait cycle and bovine serum as the lubricant. With 28 mm CoCr heads, the PE (2.5 Mrad/N2) wear rates averaged 13 mm3/10(6) cycles duration. This was considered a low value compared with the clinical model of 74 mm3/year (for 28 mm heads). Our later studies established that this low laboratory value was a consequence of the serum parameters then in use. The mating CoCr heads (with PE cups) wore at the steady state rate of 0.028 mm3/10(6) cycles. The concurrently run Metasul M-M THRs wore at the steady state rate of 0.119 mm3/10(6) cycles with high-protein serum. In the second Metasul M-M study with low-protein serum, the THR run-in rate was 2.681 mm3/10(6) cycles and steady state was 0.977 mm3/10(6) cycles. At 10 years, these data would predict a 70-fold reduction in M-M wear debris compared with the clinical PE wear model. All M-M implants exhibited biphasic wear trends, with the transition point at 0.5 x 10(6) cycles between run-in and steady state phases, the latter averaging a 3-fold decrease in wear rate. White surface coatings on implants (coming from the serum solution) were a confounding factor but did not obscure the two orders of magnitude wear performance improvement for CoCr over PE cups. The liners in the alumina head-alumina cup combination wore at the steady state rate of 0.004 mm3/10(6) cycles over 14 x 10(6) cycles duration (high-protein serum). The zirconia head-alumina cup THR combination wore at 0.174 and 0.014 mm3/10(6) cycles for run-in and steady state rates respectively (low-protein serum). The zirconia head and cup THR combination wore slightly higher initially with 0.342 and 0.013 mm3/10(6) cycles for run-in and steady state rates respectively. Other wear studies have generally predicted catastrophic wear for such zirconia-ceramic combinations. It was noted that the zirconia wear trends were frequently masked by the effects of tenacious white surface coatings. It was possible that these coatings protected the zirconia surfaces somewhat in this simulator study. The experimental ceramic Crystaloy THR had the highest ceramic run-in wear at 0.681 mm3/10(6) cycles and typical 0.016 mm3/10(6) cycles for steady state. Since these implants represented the first Crystaloy THR sets made, it was likely that the surface conditions of this high-strength ceramic could be improved in the future. Overall, the ceramic THRs demonstrated three orders of magnitude wear performance improvement over PE cups. With zirconia implants, while the cup wear was sometimes measurable, head wear was seldom discernible. Therefore, we have to be cautious in interpreting such zirconia wear data. Identifying the run-in and steady state wear rates was a valuable step in processing the ceramic wear data and assessing its reliability. Thus, the M-M and C-C THRs have demonstrated two to three orders of reduction in volumetric wear in the laboratory compared with the PE wear standard, which helps to explain the excellent wear performance and minimal osteolysis seen with such implants at retrieval operations.

Aluminum Oxide↗
PubMed2000

Transplacental effects of maternal feeding with high fat diets on lipid exchange and response of the splenic lymphoid system in mice offspring exposed to low doses of carcinogen.

We studied whether feeding pregnant female mice with different fats affects lipid exchange and activity of the splenic lymphoid system in offspring exposed to low doses of carcinogen. Female mice were fed diets with either 7% or 15% corn oil or olive oil. The 4-week-old offspring of these mice were transferred to a chow diet, and exposed to a low dose of the carcinogen, dimethylbenz(a)antracene (2 mg/kg). Results of experiments were studied 5 months later. Concentrations of polyunsaturated linoleic and oleic acids were determined in the blood and liver of mothers and offspring. The activity of the splenic immune system in offspring was studied using immunohistochemical methods for evaluating the number of different types of lymphocytes (B and T cells), mitotic and apoptotic indexes and the number of Fas-positive lymphocytes. Serum concentrations of the fatty acids examined were unchanged in the blood of the mothers and their offspring. Concentration of both linoleic and oleic acids was significantly higher in the liver of mothers fed the 15% olive-oil or corn-oil diets. This high level was maintained in linoleic acid in offspring of mothers fed the 15% olive-oil diet. Spleen weight was higher in offspring of mothers fed a 15% corn-oil diet compared to those fed the 7% corn-oil diet. The 15% olive-oil diet slightly decreased the weight of the spleen compared to counterparts fed the 15% corn-oil diet. Immunohistochemical studies showed that the olive diet, partially of 15%, significantly stimulated B-cell blast transformation. The finding reflects the reaction of B lymphocyte-producing splenic zones to the carcinogenic effect, though to a weak extent. T lymphocyte-producing zones did not respond to the diets studied, probably due to the weak carcinogenic effect and lack of tumor appearance. The Fas activity of both B and T cells in the spleen was stimulated by the carcinogen and enhanced by feeding the mothers on the olive-oil diet. Maternal feeding with a diet rich in olive oil before pregnancy results in stimulation of morphological and functional attributes of the splenic immune system of the offspring, particularly related to producing of B lymphocytes.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1999

GTP hydrolysis by arf-1 mediates sorting and concentration of Golgi resident enzymes into functional COP I vesicles.

Upon addition of GTPgammaS to in vitro budding reactions, COP I vesicles form but retain their coat, making them easy to isolate and analyze. We have developed an in vitro budding assay that reconstitutes the formation of COP I-derived vesicles under conditions where GTP hydrolysis can occur. Once formed, vesicles are uncoated and appear functional as they fuse readily with acceptor membranes. Electron microscopy shows a homogeneous population of uncoated vesicles that contain the medial/trans Golgi enzyme alpha1, 2-mannosidase II. Biochemical quantitation of vesicles reveals that resident Golgi enzymes are up to 10-fold more concentrated than in donor membranes, but vesicles formed in the presence of GTPgammaS show an average density of resident Golgi enzymes similar to that seen in donor membranes. We show that the sorting process is mediated by the small GTPase arf-1 as addition of a dominant, hydrolysis-deficient arf-1 (Q)71(L) mutant produced results similar to that of GTPgammaS. Strikingly, the average density of the anterograde cargo protein, polymeric IgA receptor, in COP I-derived vesicles was similar to that found in starting membranes and was independent of GTP hydrolysis. We conclude that hydrolysis of GTP bound to arf-1 promotes selective segregation and concentration of Golgi resident enzymes into COP I vesicles.

ADP-Ribosylation Factor 1↗
PubMed1999

Heterogenous susceptibility to CD95-induced apoptosis in melanoma cells correlates with bcl-2 and bcl-x expression and is sensitive to modulation by interferon-gamma.

The expression and functionality of the Fas receptor (CD95/APO-1) play an important role for the maintenance of tissue homeostasis. Various types of tumor cells have been shown to escape immune recognition by constitutive resistance to CD95-mediated apoptosis. Furthermore, several apoptosis-related proteins have been reported to influence CD95 sensitivity. We tested an unselected panel of 11 melanoma cell lines for sensitivity to CD95 and the corresponding expression of CD95, CD95L, bcl-2, bcl-x, bcl-xS, bax and FLIP proteins. Despite detection of CD95 cell-surface expression in 9 out of the 11 cell lines tested, only 3 melanoma cell lines were sensitive to anti-CD95-MAb-induced cell death. Apoptosis-related proteins CD95L, bcl-2, bcl-x, bcl-xS and bax were found to be heterogenously expressed in different melanoma cell lines tested. The susceptibility of melanoma cells to anti-CD95-MAb-mediated apoptosis was associated with low protein expression of both bcl-2 and bcl-x. The level of CD95 cell-surface expression in melanoma cells was no indicator for CD95 sensitivity. Furthermore, FLIP protein was detectable in 7 out of the 11 cell lines, but showed no correlation to CD95 sensitivity. Certain cytokines have been described as modulating the susceptibility of tumor cells to CD95-induced cell death. Since IFN-alpha was proved to be clinically efficient in melanoma therapy, we tested whether interferons have the ability to induce sensitivity to CD95 in primarily resistant melanoma cell lines. Here we show that IFN-gamma, but not IFN-alpha, is able to increase the susceptibility of sensitive cell lines and to induce CD95 sensitivity in resistant melanoma cell lines, accompanied by up-regulation of the protein expression level of CD95 and/or bcl-xS.

Apoptosis↗
PubMed1999

Expression of p53 and mdm2 mRNA and protein in colorectal carcinomas.

The aim of our study was to investigate the expression of p53 and mdm2 mRNA and protein in colorectal adenocarcinoma. For the detection of mRNA, 60 fresh frozen human tumour samples and 12 samples of corresponding normal tissue were examined. After total RNA extraction, reverse transcription (RT) was performed followed by cDNA amplification with specific primers using RT-polymerase chain reaction (PCR). Immunohistochemical detection of protein was examined in 81 formalin-fixed and paraffin-embedded human tumour specimens as well as 15 samples of adjacent normal colorectal tissue. p53 mRNA was detected in 80% (48/60) of the tumours and in 67% (8/12) of normal tissue samples; 87% (52/60) of tumours had mdm2 mRNA in contrast to only 17% (2/12) of normal tissue specimens. Nuclear p53 protein expression was observed in 52% (42/81) of the tumour specimens and in none of the 15 normal specimens, whereas mdm2 protein was found in the nucleus (31%, 25/81) and also in the cytoplasm (86%, 70/81) of tumour samples. In normal tissue, mdm2 protein expression was only observed in the cytoplasm (13%, 2/15) and not in the nucleus. There was a significant correlation between coexpression of p53 and mdm2 protein and the occurrence of lymph node metastases (P = 0.03) as well as between p53 protein expression and the occurrence of distant metastases (P = 0.007). Additionally, significant associations were found between p53 mRNA and p53 protein, p53 mRNA and mdm2 mRNA or protein, and also between mdm2 mRNA and mdm2 protein expression, supporting the existence of a regulatory mechanism involving p53 and mdm2.

Adult↗
PubMed1999

A multi-modality assessment of peripheral nerve function in organophosphate-pesticide applicators.

Health effects from chronic, low-level exposure to organophosphate pesticides have not been studied extensively and are not well-established. This report follows up a study in New York State in which a cohort of 90 male pesticide applicators were found to have increased vibration sensitivity thresholds, compared with a matched sample drawn from the general population. This investigation examined the nature and extent of peripheral nerve abnormalities in a small subgroup of the original cohort. Of the nine subjects studied, four had clinical evidence of peripheral neuropathic dysfunction, and one who was normal physiologically showed electrophysiological abnormalities. The remaining four showed no clinical, electrophysiologic, or quantitative signs or other abnormalities. This study adds to the growing evidence that organophosphates are toxic to the peripheral nervous system at levels of exposure that do not induce acute or subacute symptomatology.

Adult↗
PubMed1999

Asthma hospitalization rates and socioeconomic status in New York State (1987-1993).

This study examined the geographic distribution of asthma hospitalizations in New York State (NYS) and its association with socioeconomic status. Statewide asthma hospitalization data (1987-1993) were merged with 1990 census data by residential zip code. The asthma hospitalization rate increased in NYS from 1987 (2.54 per 1000) through 1993 (2.87 per 1000) and the increase is largely attributable to increases for children 4 years old and younger. The risk factors for asthma admission varied in different areas. However, rates of hospitalization because of asthma were generally higher in the zip codes areas with higher proportions of poverty, unemployment, poorly educated residents, African-Americans, and Hispanics.

Adolescent↗
PubMed1999

Metal-on-metal bearing in hip prosthesis generates 100-fold less wear debris than metal-on-polyethylene.

Aseptic loosening due to osteolysis in total hip replacement has been related to wear debris released from prosthetic components. Retrospective longterm observations of patients with the metal-on-metal prosthesis has shown long-term survivorship and good mechanical performance. Thus, the new and modified metal-on-metal prosthesis has been introduced on the market. Historical clinical data from the 1st generation metal-on-metal hip prosthesis may not be relevant for the 2nd generation of metal-on-metal hip prosthesis. Therefore, preclinical testing of the prosthesis must be conducted before clinical evaluation. We assessed the tribological performance of the metal-on-metal prosthesis versus the metal-on-polyethylene prosthesis introduced on the market as Metasul and Protasul, respectively. In a 12-channel joint simulator, 6 metal-on-metal bearing and 3 metal on polyethylene prostheses were tested, with the same number of corresponding soak controls. The wear was assessed gravimetrically. The "steady-state" wear-rates from the metal-on-metal prosthesis were almost 100 times less than that from the metal-on-polyethylene prosthesis. The tribological wear performance of the metal-on-metal hip prosthetic system is promising.

Hip Prosthesis↗
PubMed1998

Vagal efferent and afferent innervation of the rat esophagus as demonstrated by anterograde DiI and DiA tracing: focus on myenteric ganglia.

Anterograde tracing with the carbocyanine tracer DiI and the aminostyrol derivative DiA was used to selectively label fibers from the nucleus ambiguus, dorsal motor nucleus and nodose ganglion, respectively, terminating in the rat esophagus, and to compare them with the innervation of the gastric fundus in the same animals. Ambiguus neurons terminated on motor endplates distributed mainly to the ipsilateral half of the esophagus. There was no evidence of preganglionic innervation of myenteric ganglia from ambiguus neurons. Neurons of the dorsal motor nucleus supplied sparse fibers to only about 10% of enteric ganglia in the esophagus while they innervated up to 100% of myenteric ganglia in the stomach. Neurons of the nodose ganglion terminated profusely on more than 90% of myenteric ganglia of the esophagus and on about 50% of ganglia in the stomach. Afferent vagal fibers were also frequently found in smooth muscle layers starting at the esophago-gastric junction. In contrast, they were extremely rare in the striated muscle part of the esophagus. These morphological data suggest a minor influence of neurons of the dorsal motor nucleus and a prominent influence of vagal afferent terminals onto myenteric neurons in the rat esophagus.

Animals↗
PubMed1998

Parathyroid hormone-related protein (1-37) induces cAMP response in human osteoblast-like cells.

During recent years parathyroid hormone-related protein (PTHrP) research has been focused on the physiological functions of different fragments of the PTHrP molecule. Here we demonstrate that PTHrP (1-37) induced cyclic adenosine monophosphate (cAMP) response in primary human osteoblast-like cells, which were well characterized by the presence of alkaline phosphatase activity and osteocalcin production after stimulation with 1,25-dihydroxyvitamin D3. However, there was no cAMP response to PTHrP (58-77). Furthermore, the response to PTHrP (1-37) was dose dependent, with a significant increase at 1 nM. The presence of PTHrP (1-37)-induced cAMP response in human osteoblast-like cells implies that aminoterminal PTHrP fragments may exert important functions in the bone.

Adolescent↗
PubMed1998

Direct and indirect costs of chickenpox in young children.

OBJECTIVE: To estimate the medical and economic or societal costs of chickenpox in young children using a descriptive study METHODS: Children under 5 years of age attending 124 Sydney childcare centres who were reported as having chickenpox were studied to assess the costs of medication use and medical consultations, days of care missed, and parental costs resulting from lost time from work and alternate childcare costs. RESULTS: There were 174 children (92 girls and 79 boys; in three the sex was not stated) who missed a mean of 5.5 days of care because of chickenpox, currently valued at $154. Medical costs were valued at $33 per child, based on 0.97 medical visits, and topical and oral medication. Labour costs resulting from parental work absenteeism were valued at $160 or $345 depending on the method of calculation, whilst direct economic costs of $24 were incurred through use of alternate childcare arrangements. Total costs including those incurred by secondary cases and by rare hospitalisations were in the range of $393-$578 per affected child. CONCLUSIONS: Medical costs of chickenpox in children are small relative to costs incurred as a result of parental work absenteeism and to costs of foregone childcare. Ascribing precise work-related costs should take into account some capacity to make up lost work time. Such data will be required when determining the cost-benefit of childhood varicella immunisation.

Absenteeism↗