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Biomedical subjects

M Drews

Publications and source records attributed to M Drews.

At least 19 recordsLinked to original sources

Biocompatibility of supercritical CO2-treated titanium implants in a rat model.

Supercritical phase CO2 is a promising method for sterilizing implantable devices and tissue grafts. The goal of this study is to evaluate the biocompatibility of titanium implants sterilized by supercritical phase CO2 in a rat subcutaneous implantation model. At 5 weeks post implantation titanium implants sterilized by supercritical phase CO2 produce a soft tissue reaction that is comparable to other methods of sterilization (steam autoclave, ultraviolet light radiation, ethylene oxide gas, and radio-frequency glow-discharge), as indicated by the thickness and density of the foreign body capsule, although there were some differences on the capillary density. Overall the soft tissue response to the implants was similar among all methods of sterilization, indicating supercritical phase CO2 treatment did not compromise the biocompatibility of the titanium implant.

Alloys↗

Asphalt volcanism and chemosynthetic life in the Campeche Knolls, Gulf of Mexico.

In the Campeche Knolls, in the southern Gulf of Mexico, lava-like flows of solidified asphalt cover more than 1 square kilometer of the rim of a dissected salt dome at a depth of 3000 meters below sea level. Chemosynthetic tubeworms and bivalves colonize the sea floor near the asphalt, which chilled and contracted after discharge. The site also includes oil seeps, gas hydrate deposits, locally anoxic sediments, and slabs of authigenic carbonate. Asphalt volcanism creates a habitat for chemosynthetic life that may be widespread at great depth in the Gulf of Mexico.

Animals↗

Initial closed operation of the CELSS Test Facility Engineering Development Unit.

As part of the NASA Advanced Life Support Flight Program, a Controlled Ecological Life Support System (CELSS) Test Facility Engineering Development Unit has been constructed and is undergoing initial operational testing at NASA Ames Research Center. The Engineering Development Unit (EDU) is a tightly closed, stringently controlled, ground-based testbed which provides a broad range of environmental conditions under which a variety of CELSS higher plant crops can be grown. Although the EDU was developed primarily to provide near-term engineering data and a realistic determination of the subsystem and system requirements necessary for the fabrication of a comparable flight unit, the EDU has also provided a means to evaluate plant crop productivity and physiology under controlled conditions. This paper describes the initial closed operational testing of the EDU, with emphasis on the hardware performance capabilities. Measured performance data during a 28-day closed operation period are compared with the specified functional requirements, and an example of inferring crop growth parameters from the test data is presented. Plans for future science and technology testing are also discussed.

Air Conditioning↗

Local excision of rectal carcinoma not-exceeding the muscularis layer.

AIM: The aim of the study was to compare the results of treatment by local excision of two different clinical stages of the rectal cancer. MATERIAL AND METHODS: Fifty-eight patients with early rectal carcinoma were operated on during the last 26 years using different methods of local excision. The carcinomas were initially assessed as not-exceeding the muscularis layer of the rectal wall. The tumours, localized up to 12 cm from the anal margin, were removed by means of "parachute" excision (47 patients). In 6 patients, carcinoma localized in the central part of rectum, was excised by means of the Localio method. Transanal endoscopic microsurgery was applied in 5 cases of carcinoma localized on the depth of 5-20 cm from the anal margin. RESULTS: After local excision the patients were divided into two groups: I, tumours of low degree of malignancy, not exceeding submucosal layer (26 patients); II, tumours of low or median degree of malignancy with infiltration of muscularis layer (32 patients). There was a significant difference in cancer relapses between groups I and II. One patient in group I and 9 in group II developed local recurrences (P < 0.05) and 5 patients in group II had neoplastic dissemination (15.6%). CONCLUSIONS: Best results were obtained in patients with carcinoma not exceeding submucosal membrane. In cases of rectal muscular layer infiltrations, the risk of carcinoma relapses was markedly higher. The use of transanal endoscopic microsurgery has permitted removal of tumours from the upper rectum.

Adult↗

Nanoindentation properties of compression-moulded ultra-high molecular weight polyethylene.

This paper investigates the elastic modulus and hardness of untreated and treated compression-moulded ultra-high molecular weight polyethylene (UHMWPE) tibial inserts of a total knee replacement (TKR) prosthesis. Investigations were carried out at a nanoscale using a Nanoindenter at penetration depths of 100,250 and 500 nm. The nanomechanical properties of surface and subsurface layers of the compression-moulded tibial inserts were studied using the untreated UHMWPE. The nanomechanical properties of intermediate and core layers of the compression-moulded tibial insert were studied using the cryoultrasectioned and etched UHMWPE treated samples. The cryoultrasectioning temperature (-150 degrees C) of the samples was below the glass transition temperature, Tg (-122 +/- 2 degrees C ), of UHMWPE. The measurement of the mechanical response of crystalline regions within the nanostructure of UHMWPE was accomplished by removing the amorphous regions using a time-varying permanganic-etching technique. The percentage crystallinity of UHMWPE was measured using differential scanning calorimetry (DSC) and the Tg of UHMWPE was determined by dynamic mechanical analysis (DMA). Atomic force microscopy (AFM) was used to assess the effect of surface preparation on the samples average surface roughness, Ra. In this study, it was demonstrated that the untreated UHMWPE samples had a significantly lower (p < 0.0001) elastic modulus and hardness relative to treated UHMWPE cryoultrasectioned and etched samples at all penetration depths. No significant difference (p > 0.05) in elastic modulus and hardness between the cryoultrasectioned and etched samples was observed. These results suggest that the surface nanomechanical response of an UHMWPE insert in a total joint replacement (TJR) prosthesis is significantly lower compared with the bulk of the material. Additionally, it was concluded that the nanomechanical response of material with higher percentage crystallinity (67 per cent) was predominantly determined by the crystalline regions within the semi-crystalline UHMWPE nanostructure.

Biocompatible Materials↗

Effects of the sample preparation temperature on the nanostructure of compression moulded ultrahigh molecular weight polyethylene.

In this study, the effects of the sample sectioning temperature on the surface nanostructure and mechanical response of compression moulded ultrahigh molecular weight polyethylene (UHMWPE) at a nanometer scale (nanomechanical properties) have been characterized. The primary focus of this work was to determine if the sample sectioning temperature significantly changed the nanostructure of UHMWPE, while the secondary focus was to characterize the effect on the mechanical response due to the changes in the sectioned surface nanostructure. The goals of this study were: (a) to investigate the potential possibility of creating surface artefacts by the sample preparation technique by sectioning at different temperatures relative to the published range of glass transition temperatures, Tg, for PE (-12, -80 and -25 degrees C); (b) to determine the possibility of molecular orientation induced by plastic deformation of the UHMWPE sample during the process of sample preparation; (c) to measure the relative difference in nanomechanical properties owing to evolution of different nanostructures as a function of sample sectioning temperature. Field emission scanning electron microscopy (FESEM), atomic force microscopy (AFM) and nanoindentation were used to demonstrate that the sectioning temperature caused a change in nanostructure of the compression moulded UHMWPE sectioned surface, explaining the change in mechanical response to indentation at a nanoscale. In this study, it was demonstrated that significant plastic deformation occurs when a shear stress is applied between the glass or diamond blade and the UHMWPE during sample preparation under ambient conditions at a temperature of 22 degrees C. These results also suggest that an optimum sample sectioning temperature should definitely be below the measured Tg of the polymer.

Artifacts↗

Ventilator-induced lung injury upregulates and activates gelatinases and EMMPRIN: attenuation by the synthetic matrix metalloproteinase inhibitor, Prinomastat (AG3340).

Mechanical ventilation has become an indispensable therapeutic modality for patients with respiratory failure. However, a serious potential complication of MV is the newly recognized ventilator-induced acute lung injury. There is strong evidence suggesting that matrix metalloproteinases (MMPs) play an important role in the development of acute lung injury. Another factor to be considered is extracellular matrix metalloproteinase inducer (EMMPRIN). EMMPRIN is responsible for inducing fibroblasts to produce/secrete MMPs. In this report we sought to determine: (1) the role played by MMPs and EMMPRIN in the development of ventilator-induced lung injury (VILI) in an in vivo rat model of high volume ventilation; and (2) whether the synthetic MMP inhibitor Prinomastat (AG3340) could prevent this type of lung injury. We have demonstrated that high volume ventilation caused acute lung injury. This was accompanied by an upregulation of gelatinase A, gelatinase B, MT1-MMP, and EMMPRIN mRNA demonstrated by in situ hybridization. Pretreatment with the MMP inhibitor Prinomastat attenuated the lung injury caused by high volume ventilation. Our results suggest that MMPs play an important role in the development of VILI in rat lungs and that the MMP-inhibitor Prinomastat is effective in attenuating this type of lung injury.

ADAM Proteins↗

Pathways of glutamine metabolism in Spodoptera frugiperda (Sf9) insect cells: evidence for the presence of the nitrogen assimilation system, and a metabolic switch by 1H/15N NMR.

1H/15N and 13C NMR were used to investigate metabolism in Spodoptera frugiperda (Sf9) cells. Labelled substrates ([2-15N]glutamine, [5-15N]glutamine, [2-15N]glutamate, 15NH4Cl, [2-15N]alanine, and [1-13C]glucose) were added to batch cultures and the concentration of labelled excreted metabolites (alanine, NH4+, glutamine, glycerol, and lactate) were quantified. Cultures with excess glucose and glutamine produce alanine as the main metabolic by-product while no ammonium ions are released. 1H/15N NMR data showed that both the amide and amine-nitrogen of glutamine was incorporated into alanine in these cultures. The amide-nitrogen of glutamine was not transferred to the amine-position in glutamate (for further transamination to alanine) via free NH4+ but directly via an azaserine inhibitable amido-transfer reaction. In glutamine-free media 15NH4+ was consumed and incorporated into alanine. 15NH4+ was also incorporated into the amide-position of glutamine synthesised by the cells. These data suggest that the nitrogen assimilation system, glutamine synthetase/glutamate synthase (NADH-GOGAT), is active in glutamine-deprived cells. In cultures devoid of glucose, ammonium is the main metabolic by-product while no alanine is formed. The ammonium ions stem both from the amide and amine-nitrogen of glutamine, most likely via glutaminase and glutamate dehydrogenase. 13C NMR revealed that the [1-13C] label from glucose appeared in glycerol, alanine, lactate, and in extracellular glutamine. Labelling data also showed that intermediates of the tricarboxylic acid cycle were recycled to glycolysis and that carbon sources, other than glucose-derived acetylCoA, entered the cycle. Furthermore, Sf9 cell cultures excreted significant amounts glycerol (1.9-3.2 mM) and ethanol (6 mM), thus highlighting the importance of sinks for reducing equivalents in maintaining the cytosolic redox balance.

Alanine↗

Expression of keratinocyte growth factor and its receptor in colorectal cancer.

BACKGROUND AND AIMS: The mesenchymal derived keratinocyte growth factor stimulates growth, differentiation and migration of intestinal epithelial cells. In the human gastrointestinal tract an overexpression of this growth factor has been reported in inflammatory bowel disease and pancreatic cancer. In the present study we investigated expression patterns of keratinocyte growth factor and receptor in normal and neoplastic colonic mucosa and in metastases. Furthermore, biological effects on normal intestinal and colorectal cancer cell lines were determined. MATERIALS AND METHODS: Expression patterns were analysed at the mRNA level by reverse transcription-polymerase chain reaction (RT-PCR) and at the protein level by Western blotting. Localization of ligand and receptor in normal intestinal mucosa and cancer tissue was investigated by immunohistochemistry. Mitogenic effects of keratinocyte growth factor were assayed by [3H]thymidine incorporation in normal (Intestine-407, IEC-6, IEC-18) and colorectal cancer cell lines (Colo320, LoVo, SW403, SW707). RESULTS: mRNA expression of keratinocyte growth factor and receptor was detected in the majority of normal and cancer samples without significant alterations. At the protein level keratinocyte growth factor expression did not differ between normal and malignant specimens, whereas protein expression of the receptor was increased up to twofold in well- to moderately differentiated colorectal cancers. DNA synthesis was significantly stimulated by keratinocyte growth factor in all three normal intestinal cell lines, whereas this growth factor did not significantly alter the [3H]thymidine incorporation in the colorectal cancer cell lines. CONCLUSION: Keratinocyte growth factor and its receptor were detected in the majority of samples from normal and neoplastic colonic mucosa, with an overexpression of the receptor seen in the more differentiated tumour samples. Keratinocyte growth factor is a strong mitogen for normal intestinal cells, whereas it is less effective in neoplastic cells.

Blotting, Western↗

Endoscopical and histological aspects of inflammatory changes in J-pouch mucosa.

The aim of the study was endoscopic and histological evaluation of mucosal inflammatory changes in the ileal reservoir after restorative proctocolectomy with ileoanal anastomosis (IPAA) because of FAP (27 patients) and ulcerative colitis (34 patients). Endoscopic symptoms of pouchitis (edema, granularity, contact bleeding, loss of vascular pattern, mucus, erosions) were found in 13 patients (4 were operated on because of FAP, 9 because of UC). A statistically significant difference (p < 0.0001) was found between endoscopic inflammatory index in UC (4.0 +/- 0.5) and in FAP (1.00 +/- 0.00). The endoscopic changes were correlated with the Moskowitz histological classification, in 12 acute score and in 6 chronic score were above 4 points. In 18 patients histological diagnosis of pouchitis was made (5 in FAP, 13 in UC). Acute pouchitis occurred in 12 patients and chronic in 6. In one patient histological changes resembled Crohn's disease. Regular endoscopic control with histological examination and verification of inflammatory lesions in the ileal reservoir is necessary.

Adenomatous Polyposis Coli↗

Regulation of gelatinases in human airway smooth muscle cells: mechanism of progelatinase A activation.

Matrix metalloproteinases (MMPs) play an important role in tumor metastasis and invasion, inflammatory tissue destruction and remodeling, wound healing, and angiogenesis. The 72-kDa gelatinase A is the most widely distributed of all the MMPs, and along with the 92-kDa gelatinase B, both play an important role in the turnover of basement membrane. The role of MMPs in chronic airway inflammation and remodeling has received scant attention. In this study, we sought to examine the release and activation of gelatinases from human airway smooth muscle (ASM) cells and the effect of tumor necrosis factor-alpha and phorbol 12-myristate 13-acetate (PMA) on this release and activation. The role of membrane type 1 MMP (MT1-MMP) and tissue inhibitor of MMP (TIMP)-2 in activating progelatinase A has been explored. We have demonstrated, using human airway smooth muscle cells in culture, that 1) ASM releases gelatinase A constitutively and when stimulated with PMA and tumor necrosis factor-alpha releases gelatinase B, and the release of gelatinase B is protein kinase C dependent because it is blocked by H-7 and staurosporin; 2) treatment of ASM cells with PMA or concanavalin A failed to activate progelatinase A despite these agents increasing cell expression of MT1-MMP; and 3) the inability of ASM cell membranes to activate progelatinase A is most likely secondary to the high levels of TIMP-2 on the cell membrane. In conclusion, our results demonstrate that human ASM cells constitutively secrete progelatinase A and when stimulated with proinflammatory mediators secrete gelatinase B. The released gelatinases A and B may be important factors in the airway remodeling that occurs in asthma.

Cell Membrane↗

Effect of Helicobacter pylori infection, smoking and dietary habits on the occurrence of antrum intestinal metaplasia. Clinico-epidemiological study in Poland.

The purpose of the study was to assess risk factors for intestinal metaplasia arising from H. pylori-related chronic gastritis in a subset of the population referred to endoscopic examinations due to dyspeptic complaints. We aimed specifically to establish whether H. pylori itself may be responsible for the occurrence of intestinal metaplasia and to which extent the metaplasia may be associated with life style factors such as cigarette smoking, alcohol consumption or dietary habits. The study was carried out in a sample of 1290 outpatients referred for the first time to gastroenterologic outpatient clinics in 6 university centers in Poland. The study methods covered standardized health interviews, endoscopy and histology of gastric antral specimens taken at endoscopy. The interviews performed by trained interviewers sought information on tobacco and alcohol intake, diet, socioeconomic status, and other variables. In non-ulcer dyspepsia subjects there was 54.9% H. pylori related gastritis and 25.1% of non-H. pylori-related gastritis. The corresponding rates in the group of ulcer dyspepsia were 67.5% and 20.5%. The increased risk of chronic gastritis in antrum was associated with Helicobacter pylori infection (OR = 2.28; 95% CI:1.93-2.69), and with gastric peptic ulcer (OR = 1.88; 95% CI:1.20-2.94). In the non-ulcer dyspepsia the prevalence of metaplasia was 11.1% and in ulcer dyspepsia 19.7%. The risk of intestinal metaplasia within antrum depended greatly upon the presence of gastric peptic ulcer (OR = 3.85; 95% CI:2.35-6.32) and increased with age (OR = 1.05; 95% CI:1.04-1.07), smoking cigarettes currently or in the past (OR = 1.42; 95% CI:1.10-1.84), higher frequency of drinking vodka (OR = 1.32, 95% CI:1.01-1.75) and antral chronic gastritis (OR = 1.31; 95% CI:1.00-1.70), however, it was inversely related to daily consumption of fresh fruits or vegetables (OR = 0.59; 95% CI:0.38-0.93). The results of the study suggest that there is no sufficient evidence supporting the hypothesis about an association between H. pylori gastritis and intestinal metaplasia, however, the transition of gastritis to metaplasia depends greatly on life style factors such as cigarette smoking or vodka drinking and is impeded by daily consumption of fresh fruits or vegetables.

Alcohol Drinking↗

[Typing of methicillin resistant strains of S. haemolyticus isolated from patients and from the hospital ward environment].

Biotyping, antibiograms and fingerprinting were used to determine the relation of 16 methicillin-resistant S. haemolyticus isolated from drains in patients who underwent intraabdominal surgery to 9 methicillin-resistant strains of S. haemolyticus isolated at the same time from hospital environment. The comparison of biochemical properties of the examined strains showed a large variety of biochemical profiles as well as antibiotic patterns of susceptibility. The differences in sensitivity to the antibiotics used were not distinct. Biotyping and antibiograms did not permit determination of the relation of the investigated strains. Only the results of fingerprinting allowed for the division of the 25 examined strains into three genotypes demonstrating three main patterns of PCR products. 16 strains of 25 showed the same pattern of PCR products. This results suggests the presence of a source of infection on the clinical ward. A nurse may have been the source of infection because the same genotype of S. haemolyticus was isolated from her nasal anterior as from the majority of patients.

Cross Infection↗

[Peritonitis determined by the site of intra-abdominal surgery].

The aim of this study was to determine bacterial flora infecting the peritoneal cavity during intraabdominal surgery by site of operation. Three groups of patients were examined. 29 patients who underwent surgery on the stomach, duodenum, biliary tract or pancreas, 15 patients operated on because of acute appendicitis and 63 patients operated on because of colon or rectum tumours. At the end of the operation but before closure cultures were obtained by swab from the completed anastomosis site. Samples were placed into transport medium and transported promptly to the laboratory. The results of the bacteriological examinations showed that the peritoneal cavity of all patients operated on were infected with bacteria characteristic for the digestive tract, especially by Enterobacteriaceae spp., Enterococcus spp. and Bacteroides spp. From patients operated on because of rectum or colon tumours 3 or 4 bacterial species were isolated most often and they were often infected with P. aeruginosa and C. albicans. This was in contrast to patients from the other groups. In patients infected with polymicrobial flora, B. fragilis and E. coli or enterococci and E. coli and enterococci were most often seen.

Anastomosis, Surgical↗

Increased serum stromelysin-1 levels in systemic lupus erythematosus: lack of correlation with disease activity.

OBJECTIVE: In view of evidence that stromelysin-1 and collagenase-1 are involved in tissue injury in inflammatory joint diseases, we sought to determine whether matrix metalloproteinases (MMP) are implicated in the pathophysiology of systemic lupus erythematosus (SLE). METHODS: Seventy-three patients with SLE and 39 healthy subjects were evaluated. Serum levels of MMP and tissue inhibitor of metalloproteinases were measured. RESULTS: Serum stromelysin-1 levels were significantly increased in patients with SLE (416+/-252 ng/ml) compared to healthy subjects (125+/-93 ng/ml). No correlation between serial measurements of stromelysin-1 and disease activity in SLE patients was noted. Serum collagenase-1, gelatinase A, and TIMP-1 levels were not increased in SLE. CONCLUSION: Serum concentrations of stromelysin-1 are increased in SLE, but the levels do not correlate with disease activity.

Disease Progression↗

The propeptide domain of membrane type 1 matrix metalloproteinase is required for binding of tissue inhibitor of metalloproteinases and for activation of pro-gelatinase A.

Activation of secreted latent matrix metalloproteinases (MMPs) is accompanied by cleavage of the N-terminal propeptide, thereby liberating the active zinc from binding to the conserved cysteine in the pro-domain. It has been assumed that an analogous mechanism is responsible for the activation of membrane type 1 MMP (MT1-MMP). Using recombinant wild-type MT1-MMP cDNA and mutant cDNAs transfected into COS-1 cells lacking endogenous MT1-MMP, we have examined the function of the propeptide domain of MT1-MMP. MT1-MMP was characterized by immunoblotting, surface biotinylation, gelatin substrate zymography, and 125I-tissue inhibitor of metalloproteinases 2 (TIMP-2) binding. In contrast to wild-type MT1-MMP-transfected COS-1 cells, transfected COS-1 cells containing a deletion of the N-terminal propeptide domain of MT1-MMP or a chimeric construction (substitution of the pro-domain of MT1-MMP with that of collagenase 3) were functionally inactive in terms of binding of 125I-labeled TIMP-2 to the cell surface and initiating the activation of pro-gelatinase A. These results support the concept that in its native plasma membrane-inserted form, the pro-domain of MT1-MMP plays an essential role in TIMP-2 binding and subsequent activation of pro-gelatinase A.

Enzyme Activation↗