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Biomedical subjects

M Schmidt

Publications and source records attributed to M Schmidt.

At least 469 records · Page 26Linked to original sources
PubMed1996

Histochemical characterisation of the pretecto-geniculate projection in kitten and adult cat.

Neurons in the pretectal nuclear complex projecting to the dorsal lateral geniculate nucleus (LGNd) in cat were studied at different postnatal ages by using a combination of retrograde tracing techniques with glutamic acid decarboxylase (GAD) in situ hybridisation and calbindin-D28K (CALB) and parvalbumin (PARV) immunocytochemistry. About 50% of the neurons retrogradely labelled from the LGNd expressed GAD mRNA and this percentage did not change during postnatal development. LGNd-projecting neurons were never observed to be CALB- or PARV-immunoreactive.

Animals↗
PubMed1996

Apoptosis and immunohistochemical bcl-2 expression in colorectal adenomas and carcinomas. Aspects of carcinogenesis and prognostic significance.

BACKGROUND: The bcl-2 oncoprotein confers a survival advantage to cells by inhibiting programmed cell death (PCD) or apoptosis. Overexpression of bcl-2 probably plays a role in colorectal carcinogenesis. The aims of our study were to determine bcl-2 expression and PCD index in colorectal adenomas and carcinomas in correlation with p53 expression, Ki-67 index, and histopathology, and to test their prognostic significance in patients with colorectal carcinomas. METHODS: Immunohistologic staining for bcl-2 (MoAb clone 124), the proliferation-associated Ki-67 antigen (MoAb MIB1), and p53 (MoAb DO1) was performed on archival material from 44 colorectal adenomas and 95 adenocarcinomas (TNM classifications pT2 and -3, pN0, and M0). The PCD was visualized by enzymatic detection of DNA fragmentation. RESULTS: bcl-2 was expressed in 86% of the adenomas and 67% of the carcinomas. Mean PCD and Ki-67 rates were 1.7 +/- 0.14% and 35 +/- 13% in adenomas and 1.9 +/- 0.15% and 28 +/- 14% in carcinomas, respectively. In carcinomas, bcl-2 expression was correlated with a low PCD index (< 1.5%; P = 0.005). Furthermore, a high Ki-67 index (> or = 25%) was associated with a high PCD index (> or = 1.5%; P < 0.0001). p53 accumulation was seen in 16% of adenomas and in 42% of carcinomas, and did not correlate with bcl-2 expression or PCD index. In the univariate analyses, significantly longer disease free survival intervals were observed in three groups: all patients with bcl-2-positive carcinomas (P < 0.05); the subgroup of carcinomas with bcl-2 expression and low PCD index (P = 0.037); and the subgroup of bcl-2-positive and p53-negative carcinomas (P = 0.021). In the multivariate analysis, however, only tumor stage and p53 expression were independent risk factors for prognosis. CONCLUSIONS: Our data indicate that bcl-2 expression is characteristic of the early phase of colorectal carcinogenesis. Its physiologic function as an inhibitor of PCD is preserved in most colorectal carcinomas, whereas p53 is apparently not involved in the regulation of PCD in colorectal neoplasias. bcl-2 expression in colorectal carcinomas is associated with a better clinical course. This correlation became even more evident in the subgroups of patients with carcinomas that also had low PCD index or lacked p53 immunoreactivity.

Adenoma↗
PubMed1996

Characterization of a plastid-specific HSP90 homologue: identification of a cDNA sequence, phylogenetic descendence and analysis of its mRNA and protein expression.

The isolation of cDNAs is described which encode the complete sequence of a precursor protein for a HSP90 homologue consisting of an N-terminal transit peptide of 5850 Da and a mature protein (cpHSP82) of 82 260 Da, located in the plastids of rye leaves (Secale cereale). Hybridization analysis indicated the presence of a single gene in the DNA of rye and a transcript size of 2.8 kb. A phylogenetic tree constructed on the basis of sequence comparisons for HSP90 homologues from different species and compartments indicated that the plastidic HSP82 from rye was more closely related to an eubacterial protein than to HSP90 homologues of the cytosol or ER from both plants and animals. The results suggest that during chloroplast evolution the gene for cpHSP82 was transferred to the nucleus from a prokaryotic endosymbiont. Immunoblots with specific antibodies and Percoll gradient-purified organelles confirmed the location of cpHSP82 in chloroplasts or non-green plastids. In green rye leaves cpHSP82 was constitutively expressed and equally distributed among tissues of different age. The expression of cpHSP82 was enhanced within 2 h by exposure to 42 degrees C. The cpHSP82 transcript and protein were much more strongly expressed in non-green tissues, such as etiolated, 70S ribosome-deficient 32 degrees C-grown, or herbicide-bleached, than in normal green leaves. Also chromoplasts from the pericarp of tomato fruits contained high levels of a HSP90 polypeptide while a photosynthetic protein, the large subunit of ribulose-1,5-bisphosphate carboxylase was largely degraded during ripening.

Amino Acid Sequence↗
PubMed1996

A role for Rho in receptor- and G protein-stimulated phospholipase C. Reduction in phosphatidylinositol 4,5-bisphosphate by Clostridium difficile toxin B.

Receptors coupled to heterotrimeric guanine nucleotide-binding proteins (G proteins) activate phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2)-hydrolyzing phospholipase C (PLC) enzymes by activated alpha of free beta gamma subunits of the relevant G proteins. To study whether low molecular weight G proteins of the Rho family are involved in receptor signaling to PLC, we examined the effect of Clostridium difficile toxin B, which glucosylates and thereby inactivates Rho proteins, on the regulation of PLC activity in human embryonic kidney (HEK) cells stably expressing the m3 muscarinic acetylcholine receptor (mAChR) subtype. Toxin B treatment of HEK cells did not affect basal PLC activity, but potently and efficiently inhibited mAChR-stimulated inositol phosphate formation. PLC activation by the endogenously expressed thrombin receptor and by the direct G protein activators, A1F-4 and guanosine 5'-[gamma-thio]triphosphate (GTP gamma S), studied in intact and permeabilized cells, respectively, were also inhibited by toxin B treatment. C3 exoenzyme, which ADP-ribosylates Rho proteins, mimicked the inhibitory effect of toxin B on GTP gamma S-stimulated PLC activity. Finally both toxin B and C3 exoenzyme significantly reduced, by 40 to 50%, the total level of PtdIns(4,5)P2 in HEK cells, without affecting the levels of phosphatidylinositol and phosphatidylinositol 4-phosphate. Accordingly, When PLC activity was measured with exogenous PtdIns(4,5)P2 as enzyme substrate, Ca(2+)- as well as GTP gamma S- or A1F-4-stimulated PLC activities were not altered by prior toxin B treatment. In conclusion, evidence is provided that toxin B and C3 exoenzyme, apparently by inactivating Rho proteins, inhibit G protein-coupled receptor signalling to PLC, most likely by reducing the cellular substrate supply.

ADP Ribose Transferases↗
PubMed1996

DNA ploidy and MYC DNA amplification in ovarian carcinomas. Correlation with p53 and bcl-2 expression, proliferative activity and prognosis.

There is increasing evidence that DNA ploidy is a prognostic factor in ovarian carcinomas, but it is uncertain whether MYC DNA amplification is an epiphenomenon of DNA nondiploidy or a distinct biological change with an impact on the clinical course of the disease. To clarify these issues we analysed DNA ploidy by flow and image cytometry and MYC copy number by polymerase chain reaction in archival material from ovarian carcinomas with known follow up. The results were compared with proliferative activity (Ki67 index) and p53 and bcl-2 expression. DNA cytometry revealed nondiploidy in 84 of 144 cases (58.3%). Nondiploidy was statistically significantly correlated with histological tumour type, histological grade, Ki67 index > 10%, FIGO stage, presence of residual tumour after debulking surgery and adverse postoperative outcome. Furthermore, DNA nondiploidy was associated with p53 accumulation. We found that 84.9% of the p53-positive cases were nondiploid. This points to the paramount importance of wild type p53 for the maintenance of genome integrity in this tumour type. MYC DNA amplification was seen in 33.8% (26/77 cases) of ovarian carcinoma. There was no correlation between MYC DNA amplification and histological tumour type, histological grade, FIGO stage, DNA ploidy, proliferative activity or prognosis. However, when p53 and bcl-2 expression was taken into account, a statistically significant correlation between gene alteration or expression patterns and histological tumour type was revealed. The group of mucinous carcinomas demonstrated both MYC DNA amplification and strong bcl-2 expression in 50% and contained the largest fraction of cases without aberration (37.5%). Endometrioid carcinomas were characterized by strong bcl-2 expression in 85%, whereas serous and undifferentiated carcinomas predominantly exhibited p53 alterations, frequently accompanied by bcl-2 overexpression or MYC DNA amplification. Thus, in interaction with other genes MYC DNA amplification may play a role in the determination of the varying differentiation patterns of ovarian carcinomas.

Aged↗
PubMed1996

Comparison of the expression of a plastidic chaperonin 60 in different plant tissues and under photosynthetic and non-photosynthetic conditions.

A partial cDNA which codes for the beta-subunit of a plastidic chaperonin 60 (cpn60-beta) from rye (Secale cereale L.) leaves was identified and sequenced, except for 46 amino acids of the N-terminus of the mature protein and the transit sequence. This is the first cpn60-beta sequence determined for a monocotyledonous plant. Specific antibodies against cpn60-beta were affinity-purified from an antiserum raised against the total soluble protein fraction of ribosome-deficient plastids. The localization of cpn60-beta in chloroplasts or non-green plastids was confirmed by immunodetection in Percoll gradient-purified organelles. The expression and occurrence of cpn60-beta was analysed by immunoblotting with the specific antibodies and Northern hybridization. The cpn60-beta protein was constitutively expressed in various green and non-green tissues. It was evenly distributed along the major part of a rye leaf, while highest transcript levels occurred in the youngest and oldest leaf sections. The expression of the cpn60-beta protein was not enhanced by a heat-shock treatment at 42 degrees C. The cpn60-beta transcript and protein were more strongly expressed in various non-green, for instance etiolated, 70S-ribosome-deficient 32 degree C-grown, or herbicide-bleached tissues, than in green leaves of rye. A rapid increase in the cpn60-beta transcript level was also observed when green leaves were transferred from light to darkness while the protein level was not affected. The dark-induced increase in the cpn60-beta transcript was totally suppressed in the presence of 2% sucrose. Inhibitor treatments suggested that the change in cpn60-beta transcript level was not related to changes of the ATP supply of the tissue. While the large subunit of the photosynthetic protein ribulose-1,5-bisphosphate carboxylase was largely degraded during ripening of tomato fruits, high levels of cpn60-beta were detected in tomato chromoplasts and in the yellow flower petals of Narcissus. Low levels of cpn60-beta were detected in root tissue.

Amino Acid Sequence↗
PubMed1996

EXAFS investigation of the active site of iron superoxide dismutase of Escherichia coli and Propionibacterium shermanii.

The local structure of the iron site in ferric superoxide dismutase from P. shermanii was analyzed by X-ray absorption spectroscopy. The metal-ligand cluster of the enzyme is found to be similar to the crystallographically investigated ferric superoxide dismutase from E. coli. At pH 6.4 the enzyme is five-fold coordinated with three histidines, an aspartate and a water molecule. The average bond lengths between the metal and the histidines are about 2.10 A, between metal and aspartate they are about 1.86 A and between metal and water 1.96 A. With an increase in pH a change in the coordination number from five to six is observed both in pre-edge peak and EXAFS spectra analysis. However, the bond lengths of the ligands do not change dramatically, they are conserved for the aspartate and increase slightly to 2.13 A for the average metal-histidine distance at pH 9.3. The observation of the increase in coordination number is correlated with a decrease in enzymatic activity which occurs in the high pH range. The zinc EXAFS spectra of P. shermanii superoxide dismutase have shown that zinc can be incorporated in the active center instead of the iron.

Amino Acid Sequence↗
PubMed1996

Response properties of relay cells in the A-laminae of the cat's dorsal lateral geniculate nucleus after saccades.

Responses of relay cells in the A-laminae of the dorsal lateral geniculate nucleus (LGNd) during spontaneous saccades and saccade-like visual stimulation were extracellularly recorded in awake cats. Ninety-six out of 137 cells recorded (42 X and 54 Y cells) were responsive during spontaneous saccadic eye movements. All Y cells and 67% of the X cells responded with burst activity, i.e. with either one or two activity peaks during and after saccades. Thirty-three percent of the X cells were inhibited during saccades. Excitatory peaks occurred at mean latencies of 33 ms and 31 ms for X and Y cells, respectively. Comparable burst responses were obtained when retinal image shifts similar to those during saccades were induced by external saccade-like stimulus movements. However, the latencies of excitatory peak activity were significantly longer to external stimuli than to the onsets of saccades. This indicates the existence of an eye movement-related input which activates LGNd relay cells in addition to the visual input. We propose that the pretectogeniculate projection may contribute to the responses of LGNd relay cells following saccadic eye movements via a disinhibitory input and that this input could be involved in intra- and postsaccadic modulations of the transfer of visual signals to visual cortex.

Animals↗
PubMed1996

Pregnancies, calves and calf viability after transfer of in vitro produced bovine embryos.

Pregnancy, parturition and calf survival following the transfer of embryos produced in vitro were monitored. A total of 44 blastocysts was transferred in pairs to 1 uterine horn ipsilateral to the corpus luteum (CL) of 22 synchronized heifers. At Day 42 of development 14 recipients (64%) were pregnant; the calving rate was also 64%. The twinning rate was 9/14 at Day 42 and 7/14 at birth, for an overall fetal mortality rate of 9%. The average gestation length was 281 and 275 d for single and twin pregnancies, respectively. Blood samples from recipients were collected for determination of bovine pregnancy associated glycoprotein (bPAG) from 2 wk after transfer and throughout the pregnancy. During the first trimester of pregnancy, the bPAG concentration was significantly higher in twin than in single bearing heifers, and the perinatal increase in bPAG was correlated positively with the total weight of the fetus(es). The percentage of male calves was 43%. The birth weight of twin individuals was 25 +/- 1 kg, which was 78% of the birthweight of the singletons (32 +/- 2 kg). One singleton calf was oversized, weighing 58 kg (80% more than the median weight of the other singletons). Stillbirths occurred in 21% of the twins, butin none of the singletons. Calf mortality during the first 14 d was higher for twins (4/11) than for singletons (1/7) due to infections and cerebellar hypoplasia. Karyotyping the calves detected no cytogenetically recognizable abnormalities. All calves were negative for BVD virus and IBR antibodies. The results of this study showed that although the incidence of fetal loss was low, there was an unacceptable high perinatal mortality of the calves. Thus it is likely that the blood supply through the placenta of animals pregnant with twins was impaired or it is possible that these fetuses and calves had increased stress susceptibility caused by the in vitro conditions. Furthermore, the birth of 1 oversized calf, 2 calves with cerebellar hypoplasia and 5 calves succumbing to infections seems to indicate that a proportion of in vitro produced calves may suffer from factors inherent in the in vitro production system.

Journal Article↗
PubMed1996

Production of a recombinant imported fire ant venom allergen, Sol i 2, in native and immunoreactive form.

BACKGROUND: The complementary DNA encoding for the important imported fire ant venom allergen, Sol i 2, has previously been cloned. The binding of human IgE antibodies to Sol i 2 has been demonstrated to be conformation-dependent. METHODS: A couple cDNA clone encoding the Sol i 2 protein sequence and its natural signal sequence has been produced by polymerase chain reaction. The clone was ligated into a pBluebac III transfer vector (Invitrogen Corp., San Diego, Calif.), and the recombinant baculovirus was isolated by plaque purification. The recombinant baculovirus was grown in Sf9 and High-Five cells (Invitrogen Corp.) in serum-free media. The recombinant Sol i 2 was isolated and characterized. RESULTS: Recombinant (r) Sol i 2 was produced in microgram/per milliliter amounts in Sf9 cells and at 30 micrograms/ml in High-Five cells. It was isolated by ultrafiltration and reverse-phase chromatography. The rSol i 2 demonstrated similar binding to natural-Sol i 2 in both a conformation-dependent ELISA assay and in RAST with sera from patients allergic to Sol i 2. The N-terminal sequence of the rSol i 2 was identical to that of the natural molecule. No significant increase in binding activity was found after treatment of rSol i 2 with protein disulfide isomerase. The binding of rSol i 2 to a conformation-dependent monoclonal antibody was lost by heating in sodium dodecylsulfate and reduction. CONCLUSION: A recombinant Sol i 2 protein was produced at high yield in a baculovirus expression system by using serum-free medium with a sequence identical to that of the natural molecule. Conformation-dependent immunologic assays indicate that the recombinant protein is produced with the native conformation.

Allergens↗
PubMed1996

Determination of substance P in human nasal lavage fluid.

The determination of substance P (SP) concentrations in human nasal lavages can be used to monitor physiological and certain pathophysiological processes in human airway mucosa. But, because of the low concentrations, immunoassays of high sensitivity are needed. Two approaches to improve the sensitivity of the radioimmunological determinations of SP are compared: increasing the sample volume and miniaturizing the assay design. The characterization of SP-like immunoreactivity (SP-LIR) in human nasal lavage was performed by investigating the immunological specificity of the antibody used in the radioimmunoassays and by reversed-phase high-performance liquid chromatography separation of the SP-LIR. SP concentrations in nasal lavages can be reliably measured by each of the two introduced RIA methods. Despite the lower detection limit of the miniaturized immunoassay (0.2 in comparison to 1.3 fmol/incubate) it is advisable to increase the sample volume in order to improve the sensitivity because of the higher precision of the determinations. SP-LIR was found in nasal lavage specimens in concentrations between 2 and 10 fmol/ml and consisted of authentic SP and, to a less extent, SP-sulfoxide.

Chromatography, High Pressure Liquid↗
PubMed1996

Targeted inhibition of tumour cell growth by a bispecific single-chain toxin containing an antibody domain and TGF alpha.

Overexpression of the epidermal growth factor receptor (EGFR) and ErbB-2 has been observed in a variety of human tumours, making these receptors promising targets for directed tumour therapy. Since many tumour cells express both ErbB-2 and EGFR and these receptors synergise in cellular transformation, therapeutic reagents simultaneously binding to ErbB-2 and EGFR might offer advantages for tumour therapy. We have previously described the potent anti-tumoral activity of a bispecific antibody toxin that contains ErbB-2- and EGFR-specific single-chain Fv (scFv) domains. Here we report the construction and functional characterisation of a novel bispecific recombinant toxin, scFv(FRP5)-TGF alpha-ETA. The fusion protein consists of the antigen-binding domain of the ErbB-2-specific MAb, FRP5, and the natural EGFR ligand, TGF alpha, inserted at different positions in truncated Pseudomonas exotoxin A. ScFv(FRP5)-TGF alpha-ETA protein displayed binding to EGFR and ErbB-2, thereby inducing activation of the receptors, which was dependent on the cellular context and the level of EGFR and ErbB-2 expression. The bispecific molecule was cytotoxic in vitro for tumour cells expressing various levels of the target receptors. In vivo scFv(FRP5)-TGF alpha-ETA potently inhibited the growth of established A431 tumour xenografts in nude mice.

ADP Ribose Transferases↗
PubMed1996

Apoptosis of monocytes cultured from long-term hemodialysis patients.

Monocyte apoptosis in vitro was studied in patients on long-term hemodialysis, CAPD, and in predialytic uremia to gain insight into the high susceptibility of these patients to infections. Monocytes from dialysis and control subjects were cultured for 24 to 120 hours in vitro to analyze the level and progression of DNA fragmentation as a hallmark of apoptosis. After an incubation time of 48 hours chromatin fragmentation of 48.5 +/- 7.7% was found in monocytes from dialysis patients, which significantly exceeded DNA fragmentation of control monocytes (23.1 +/- 9.1%; N = 12; P < 0.01). Over longer culture periods of up to 5 days, a continuous progression of apoptosis occurred with a similar slope of percent DNA fragmentation in the two studied groups. Monocyte viability was > 95% both in the dialysis and control group. Hemodialysis patients also showed elevated levels of monocyte apoptosis when programmed cell death was evaluated by transmission electron microscopy or DNA electrophoresis of cleaved chromatin. To test the functional relevance of monocyte apoptosis, a significant reduction of Candida growth inhibition by monocytes of dialysis patients was found with a strong linkage between percentage of DNA fragmentation and impaired microbicidal capacity. Monocytes obtained from patients after the hemodialysis session and from CAPD patients showed normal DNA fragmentation levels similar to controls. Differences of monocyte apoptosis between patients on cuprophane and high-flux polysulphone dialysis were not found. Uremic predialytic patients also exerted an increased monocyte DNA fragmentation of 44.2 +/- 1.5% (N = 7; P < 0.05 compared to controls). Enhanced apoptosis of uremic monocytes was accompanied by a reduced formation of TNF-alpha over 48 hours, revealing a significant negative correlation between chromatin fragmentation and monokine synthesis. Supplementation of monocyte cultures from dialysis patients with exogenous TNF-alpha turned increased apoptosis back to baseline levels, suggesting that inflammatory mediators may modulate monocyte senescence. In summary, the elevated degree of monocyte apoptosis in end-stage renal failure may contribute to the impaired cellular host defense seen in these patients.

Adult↗
PubMed1996

Characterization of different soluble TNF receptor (TNFR80) derivatives: positive influence of the intracellular domain on receptor/ligand interaction and TNF neutralization capacity.

Different soluble human TNFR80 derivatives, a solubilized form of the complete TNFR80, the TNFR80 extracellular domain, a secretory TNFR80 mutant (TR80TM-) with a deleted transmembrane region, and a TNFR80 immunoadhesin were produced in insect cells and characterized side by side with a recombinant human TNFR60 extracellular domain with respect to TNF binding affinity and neutralization of TNF bioactivity. The construct TR80TM- and the solubilized complete TNFR80 revealed a similar TNF binding and neutralization capacity, which was superior to the monovalent TNFR80 extracellular domain and comparable to the bivalent TNFR80 immunoadhesin, already known as a potent TNF antagonist. Determination of ligand off rate constants of the various receptor constructs by surface plasmon resonance revealed a correlation of low off rates with a high TNF neutralization capacity. We propose that the high TNF binding and neutralization capacity of the solubilized complete TNFR80 and TR80TM- in comparison with the monovalent extracellular TNR80 domain is due to a noncovalent self-aggregation of the receptors via their intracellular domain. This finding suggests that efficient soluble TNF antagonists can be derived from TNFR themselves without the need of construction of TNFR Ig Fc fusion proteins.

Cytotoxicity, Immunologic↗
PubMed1996

bcl-2 expression, p53 accumulation, and apoptosis in ovarian carcinomas.

Because little is known about the importance of apoptosis and its regulation in epithelial ovarian cancer, the authors looked for bcl-2 expression and p53 accumulation by immunohistochemistry in 148 ovarian carcinomas of different histologic types and stages. The number of apoptotic cells was assessed in situ by enzymatic detection of DNA fragmentation. Strong bcl-2 expression correlated with low histologic grade (P = .004) and was most often seen in endometrioid carcinomas (P = .001), whereas p53 accumulation was predominantly found in serous and undifferentiated carcinomas (P <.001) and high grade tumors (P <.001). p53 accumulation was associated with advanced tumor stage (P <.001) and the presence of residual disease after surgery (P <.001). Apoptosis increased with histologic grade (P = .012); apoptotic cells were sparse or absent in tumors of low malignant potential and mucinous carcinomas, but found in all other carcinoma types (P = .001). Apoptosis, bcl-2 expression, and p53 protein accumulation were not correlated with each other. The analysis of the postoperative course of 110 patients showed that survival depended on histologic tumor type (P = .0037), histologic grade (P = .0143), FIGO (International Federal of Gynecology and Obstetrics) stage (P = .0001), and absence or presence of postoperative residual tumor mass (P = .0001). p53 accumulation was also associated with adverse prognosis (P = .0001). However, bcl-2 positive carcinomas who had a statistically significantly better outcome than patients with p53 positive and bcl-2 negative tumors (P = .0443). Regarding FIGO stage and p53 alone in a Cox model, p53 proved to contribute additional prognostic information both in FIGO stages I/II as well as in FIGO stages III/IV. Thus, our observations point to different molecular alterations possibly underlying phenotypic diversity of ovarian carcinomas and provide clues for a better understanding of tumor progression in these neoplasms. Apoptosis plays a role in ovarian carcinomas, but seemingly is regulated in a different way than in nonneoplastic tissues.

Adenocarcinoma↗
PubMed1996

Influence of vaginal versus abdominal hysterectomy on perioperative glucose metabolism.

The aim of this study was to investigate the metabolic effects of abdominal versus vaginal hysterectomy with specific regard to perioperative glucose metabolism. Fourteen patients received either abdominal (AH, n = 7) or vaginal hysterectomy (VH, n = 7). Hepatic glucose production was measured before and 2.5 h after the operation by stable isotope technique ([6,6-2H2]-glucose). Metabolic substrates (glucose, lactate, nonesterified fatty acids [NEFA], beta-hydroxybutyrate) and hormones (insulin, glucagon, cortisol, catecholamines) were determined pre-, intra-, and postoperatively. VH induced a higher postoperative glucose concentration than the abdominal approach (VH, 148 +/- 25 mg/dL; AH, 111 +/- 16 mg/dL; P < 0.05). Since postoperative enhancement of hepatic glucose production was comparable in both groups, glucose clearance was lower after the vaginal procedure (VH, 1.7 +/- 0.3 mL.kg-1.min-1; AH, 2.1 +/- 0.3 mL.kg-1.min-1; P < 0.05). NEFA, beta-hydroxybutyrate, and catecholamines similarily increased after surgery. Cortisol levels were more increased after VH (VH, 80 +/- 26 micrograms/dL; AH, 37 +/- 14 micrograms/dL; P < 0.001). Lactate, glucagon, and insulin concentrations did not change perioperatively. The more pronounced hyperglycemic response to VH was due to lower peripheral glucose use caused by higher postoperative cortisol values. The mechanisms responsible for this marked cortisol enhancement after the vaginal operation as well as the clinical significance for patients with preexisting impaired carbohydrate tolerance, however, remained unclear and warrant further investigation.

3-Hydroxybutyric Acid↗
PubMed1996

Cobalt chromium molybdenum metal combination for modular hip prostheses.

The development of a metal combination for modular hip systems was motivated by the following observations: (1) wear particles from polyethylene acetabular components can lead to a foreign body reaction and late aseptic loosening and (2) well designed all metal hip prostheses had very low wear rates, usually causing no osteolytic problems. The following challenges had to be met: (1) metal alloy with the maximum wear resistance; (2) the optimal clearance (difference in diameter) between 28-mm ball head and acetabular component; and (3) equipping modern, modular hip systems with metal combinations while maintaining compatibility with existing components. The realization of a metal combination consisted of the stable anchoring of a standard metal lining in a polyethylene insert that, combined, is intended to provide adequate load transfer and fit to either the bone cement bed or the titanium shell. The metal lining is manufactured from a carbide containing cobalt chromium molybdenum wrought alloy (Protasul-21WF). From 1988 to 1995, approximately 40,000 metal combinations (Metasul) were implanted. From these, 44 single components, with a maximum time in situ of 5.5 years, were retrieved and examined. The total linear wear rate averaged 2 to 5 micrometers per year per component after the initial conditioning phase. Under these conditions, particle induced late aseptic loosening is not to be expected.

Biomechanical Phenomena↗