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Biomedical subjects

G Martin

Publications and source records attributed to G Martin.

At least 37 records · Page 2Linked to original sources
PubMed2003

Reactive oxygen species downregulate the expression of pro-inflammatory genes by human chondrocytes.

OBJECTIVES: To determine the regulatory effects of reactive oxygen species (ROS) on the expression by human osteoarthritic chondrocytes of interleukin (IL)-1beta, -6 and -8, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) gene in response to interleukin (IL)-1beta or lipopolysaccharide (LPS). METHODS: Human chondrocytes in monolayer culture were incubated for 3 h with ROS generating molecules such as S-nitroso-N-acetyl-D,L-penicillamine (SNAP, 100 microM), 3-morpholinosydnonimine (SIN-1, 100 microM), with chemically synthesised peroxynitrite (ONOO-, 10 microM) or hydrogen peroxide (H2O2, 100 microM). After treatment by ROS, chondrocytes were washed and then cultured for the next 24 h with or without lipopolysaccharide LPS (10 microg/ml) or IL-1beta (1.10(-11) M). IL-1beta, IL-6, IL-8, iNOS and COX-2 gene expression was analysed by real time and quantitative RT PCR. IL-6, IL-8 and prostaglandin (PG) E2 productions were assayed by specific immunoassays. Nitrite was measured in the culture supernatants by the Griess procedure. RESULTS: LPS and IL-1beta stimulated IL-1beta, IL-6, IL-8, iNOS and COX-2 gene expression. SNAP significantly downregulated LPS induced overall gene expressions, whereas SIN-1 had no effect. ONOO- inhibited iNOS and COX-2 gene expression but not that of the cytokine genes. When chondrocytes were incubated with IL-1beta, SIN-1 and ONOO dramatically decreased all gene expressions while SNAP was inefficient. H2O2 treatment inhibited both LPS and IL-1beta induced gene expressions. CONCLUSIONS: These data provide an evidence that ROS may have anti-inflammatory properties by depressing inflammatory gene expression. Further, we demonstrate that ROS effects are dependent on the nature of radical species and the signalling pathway that is activated. These findings should be taken into consideration for the management of antioxidant therapy in treatment of inflammatory joint diseases.

Cartilage, Articular↗
PubMed2003

Carbon 13 NMR spectroscopy: a powerful tool for studying renal metabolism.

Using precise examples, this paper shows that carbon 13 NMR spectroscopy in conjunction with radioactive and enzymatic methods as well as with adequate mathematical modeling of metabolic pathways allows not only to identify but also to quantify fluxes through enzymes involved in substrate and drug metabolism. Carbon 13 NMR spectroscopy is a tool of unprecedented power to unravel the complexity of renal metabolism. Currently it plays a major role in what is nowadays called metabolomics.

Animals↗
PubMed2003

Localization of crustacean hyperglycemic and vitellogenesis-inhibiting hormones in separate cell types in the protocerebrum of the woodlouse Armadillidium vulgare (Crustacea, Isopoda).

We gave an accurate immunolocalization of CHH (crustacean hyperglycemic hormone) and VIH (vitellogenesis-inhibiting hormone) in the brain and the sinus gland of the woodlouse Armadillidium vulgare. The two immune sera have been respectively raised against HPLC-purified CHH and against a small peptide derived from the N-terminus of VIH. By immunocytochemistry, we showed that CHH and VIH were synthesized in different perikarya and stored in different axon endings of the sinus gland. As in other crustacean species studied to date, CHH was located in the axon endings filled with the biggest granules. Immunoblotting confirmed that VIH was stored in the sinus glands of both the female and the male. These clear localizations of CHH- and VIH-antigens do not preclude that only one peptide is released from a given type of SG endings and do not rule out that each peptide can be involved in the control of different physiological processes.

Animals↗
PubMed2003

Thermodiffusion for the quantification of tissue perfusion in skeletal muscle--clinical evaluation in standardized traumatological procedures with tourniquet and potential application in the diagnosis of compartment syndrome.

The quantification of tissue perfusion in different parenchymal organs like liver, kidney, and brain by means of thermodiffusion has recently been validated experimentally and was introduced into clinical practice. Traumatology and plastic surgery deal as well with issues of microcirculation. Therefore, it was the aim of this study to validate thermodiffusion for use in skeletal muscle. Eighteen patients were studied during knee arthroscopic procedures that utilized a tourniquet. A thermodiffusion probe was inserted in the tibialis anterior muscle of the side under treatment. Measurement started before the initiation of limb ischemia (by tourniquet) and continued throughout the procedure until tissue perfusion returned to normal values postoperatively. Furthermore, an example of clinical applicability of this technique is given by monitoring muscle tissue perfusion in 3 patients with imminent compartment syndrome. Preoperative values of muscle tissue perfusion in the patients undergoing arthroscopic procedures were 17.74 +/- 4.27 ml/min 100 g. After initiation of tourniquet perfusion quickly decreased to 3.59 +/- 3.53 ml/min 100 g. Upon reperfusion tissue perfusion increased to values above normal for a few minutes and then returned to preischemic values of 20.86 +/- 7.01 ml/min 100 g. There was no significant difference between pre- and postoperative values (P=0.154) but tissue perfusion during tourniquet was significantly reduced (P=0.0001). In 3 patients presenting with the clinical signs of imminent compartment syndrome, thermodiffusion measurement was applied and showed microcirculatory impairment of different degrees. Fasciotomy was followed by a prompt increase of muscle microcirculation to levels slightly above normal. In summary, valid and stable measurements of tissue perfusion in skeletal muscle by means of thermodiffusion are possible under clinical circumstances. Thermodiffusion allows for on-line monitoring of muscle microcirculation, e.g., in compartment syndrome. The clinical potential of thermodiffusion measurements in trauma surgery needs further prospective evaluation.

Adult↗
PubMed2003

Pericarditis as primary manifestation of Mycobacterium bovis SSP. caprae infection.

A 76-year-old white male presented with progressive malaise, weight loss and dyspnea at rest. Echocardiography revealed a circular pericardial effusion and global hypokinesia. Pericardiocentesis showed a purulent exudate and microbiologic examination revealed Mycobacterium bovis fully sensitive to isoniazid, streptomycin, ethambutol, rifampin, and pyrazinamide. By spoligotyping the isolate could be further differentiated to M. bovis ssp. caprae. Antimycobacterial therapy was initiated but 3 weeks later the patient's circulation and renal function deteriorated and he died with clinical signs of sepsis despite intensive care treatment. Pericarditis is a rare manifestation of tuberculosis and can be fatal even when diagnosed and treated appropriately. In low incidence countries diagnosis is often delayed and even overlooked.

Animals↗
PubMed2003

Variability in determination of point of needle insertion in peripheral nerve blocks: a comparison of experienced and inexperienced anaesthetists.

Accurate identification of surface landmarks is essential for the successful performance of peripheral nerve blocks. The variability between experienced and inexperienced practitioners in identifying anatomical landmarks has not been studied previously. Anaesthetists were asked to identify the point of needle insertion for posterior lumbar plexus and sciatic nerve blocks on a volunteer using a standard textbook description. The chosen point for needle insertion was described in terms of X and Y co-ordinates, measured in millimetres, from a zero reference point marked on a volunteer's back. Fifteen experienced and 22 inexperienced anaesthetists took part in the study. The lumbar plexus block mean [range] values for the X, Y co-ordinates were 80 [62-108], 66 [46-86] and 92 [49-150], 62 [0-131] in the experienced and inexperienced groups, respectively. The sciatic nerve block X, Y co-ordinates were 77 [62-99], 70 [49-89] and 68 [29-116], 62 [26-93] in the experienced and inexperienced groups, respectively. The variance for the point of needle insertion was significantly greater in the inexperienced group (p <0.01) for both the lumbar plexus and sciatic nerve blocks. We conclude that with increasing experience, there is decreased variability in determining the point of needle insertion using anatomical landmarks.

Anesthesiology↗
PubMed2002

Evaluation of the developmental toxicity of crocetin on Xenopus.

Crocetin, a carotenoid isolated from the spice saffron, has been found to be effective in treating certain types of cancer treatable with all-trans retinoic acid (ATRA). ATRA, however, is a potent teratogen, and the possibility that crocetin may also be a teratogen becomes an important medical issue. The teratogenic potential of crocetin and ATRA were evaluated in frog (Xenopus) embryos. The data show that crocetin is a teratogen, but far less potent than ATRA. This suggests that crocetin may be a safer alternative to treat ATRA-sensitive cancers in women of childbearing age.

Animals↗
PubMed2002

Inhibition of human primary melanoma cell proliferation by histamine is enhanced by interleukin-6.

BACKGROUND: Interleukin-6 (IL-6) is a bifunctional growth factor in malignant melanoma; its expression increases during the malignant progression of the disease. Histamine, detected in large amounts in normal and pathological proliferating tissues, is an important paracrine and autocrine regulator of normal and tumour cell proliferation as well. MATERIALS AND METHODS: We investigated the presence and function of IL-6 and histamine in the WM35 primary human melanoma cell line with respect to their direct role in cell proliferation and their regulatory interactions. RESULTS: IL-6 inhibited the proliferation of WM35 melanoma cells and increased significantly the expression of histidine decarboxylase as well as histamine production. It had dose-dependent effects on the proliferation: high concentration (10-5 M) was inhibitory through H1 histamine receptors while low histamine concentration acting on H2 receptors, with a simultaneous increase of cAMP, enhanced colony formation in the monolayer. Furthermore, IL-6 increased the H1- but decreased the H2-histamine receptor expression of the melanoma cells. On the other hand, histamine was locally synthesized by the WM35 melanoma cells. CONCLUSION: We suggest that the growth arrest induced by IL-6 is in part mediated by its dual action on histamine: a shift toward H1 receptor predominance and an elevation of locally produced histamine with prevalent action on the inhibitory response triggered through the H1 receptor. These findings suggest a local cross-talk between histamine and IL-6 in the regulation of melanoma growth.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed2002

A prospective, randomized comparison of thromboelastographic coagulation profile in patients receiving lactated Ringer's solution, 6% hetastarch in a balanced-saline vehicle, or 6% hetastarch in saline during major surgery.

OBJECTIVES: To compare the effects of lactated Ringer's solution (LR), 6% hetastarch in a balanced-saline vehicle (HS-BS), and 6% hetastarch in normal saline (HS-NS) on coagulation using thromboelastography. DESIGN: Prospective, randomized double-blinded evaluation of previously published clinical trial. SETTING: Tertiary-care medical center. PARTICIPANTS: Patients undergoing elective noncardiac surgery with an anticipated blood loss >500 mL. A total of 90 patients were enrolled with 30 patients in each group. INTERVENTIONS: Patients received a standardized anesthetic. LR, HS-BS, and HS-NS were administered intraoperatively based on a fluid administration algorithm. Hemodynamic targets included maintenance of arterial blood pressure, heart rate, and urine output within a predefined range. MEASUREMENTS AND MAIN RESULTS: Thromboelastography variables for r time, k time, maximum amplitude, and alpha angle (mean +/- SD) were recorded at induction of anesthesia, at the end of surgery, and 24 hours postoperatively. Patients in the LR group showed a state of hypercoagulation at the end of surgery with reductions (p < 0.005) in r time (-3.8 +/- 6.7 mm) and k time (-1.7 +/- 2.5 mm). This state of hypercoagulation continued into the postoperative period. Patients in the HS-NS group showed a state of hypocoagulation with increases (p < 0.05) in r time (+6.2 +/- 8.5 mm) and k time (+1.7 +/- 3.9 mm) and a reduction in maximum amplitude (-8.0 +/- 9.8 mm) at the end of surgery. This state of hypocoagulation was reduced in the postoperative period. Patients in the HS-BS group showed no significant changes in coagulation status at end of surgery, with the smallest changes in r time (-0.3 +/- 4.1 mm), k time (+0.1 +/- 3.1 mm), maximum amplitude (-5.4 +/- 12.3 mm), and alpha angle (0.3 +/- 12.5 degrees ). CONCLUSION: LR-treated patients exhibited a hypercoagulative profile that persisted into the postoperative period. HS-BS administration was associated with a lesser change in the coagulation profile compared with HS-NS, which was associated with a hypocoagulative state.

Aged↗
PubMed2002

Epidermal growth factor improves nutritional outcome in a rat model of short bowel syndrome.

BACKGROUND/PURPOSE: This study investigates the effect of epidermal growth factor (EGF) on nutrient absorption in a rat model of short bowel syndrome (SBS). METHODS: Male juvenile rats underwent either transection (Sham) or ileocecal resection leaving a 20-cm jejunal remnant. Animals underwent follow-up for 10 days, and resected animals were treated with placebo or recombinant human EGF (1-53). Animals were pair fed; in vivo nutrient absorption, intestinal permeability, morphology, and total intestinal DNA and protein content were measured. RESULTS: Resected EGF-treated animals lost significantly less weight than those in the placebo group (-4.2 +/- 3 v -13.7 +/- 6.9%), absorbed significantly more 3-0 methylglucose (76.8 +/- 6.6 v 64.9 +/- 10.1%), and had reduced permeability (lactulose/mannitol ratio, 0.35 +/- 0.19 v 0.60 +/- 0.20; P <.05 for all comparisons). CONCLUSIONS: These findings show that treatment of short bowel syndrome animals with EGF reduced weight loss and improved carbohydrate absorption and intestinal permeability. These findings suggest that enteral EGF may be a useful therapy for short bowel syndrome; further studies are indicated.

Absorption↗
PubMed2002

Cimetidine and a tamoxifen derivate reduce tumour formation in SCID mice xenotransplanted with a human melanoma cell line.

Histamine is produced by many cells expressing histidine decarboxylase (HDC), the enzyme responsible for the synthesis of histamine. Since melanoma cells and tissue contain relatively large amounts of histamine, the functional significance of histamine was examined using specific antihistamines in vitro and in vivo in the human melanoma cell line HT168 and severe combined immunodeficiency (SCID) mice. It was shown that the H2 receptor antagonist cimetidine when combined with N, N-diethyl-2-[4-(phenylmethyl)phenoxy]-ethanamine-HCl (DPPE), a tamoxifen derivate, inhibits the proliferation of HT168 cells. Furthermore, it is suggested that there is a factor(s) that interferes with the exponential growth of HT168 cells xenografted to immunodeficient mice, and cimetidine and DPPE together significantly influence this factor(s). This combination of antihistamines also increases the survival of human melanoma-grafted mice. These changes are accompanied by enhanced infiltration of interferon-gamma- producing mouse macrophages into the tumour tissue. These findings suggest that two different mechanisms are probably acting concordantly: direct inhibition of tumour cell proliferation by the H2 receptor antagonists, and activation of the local immune response characterized by interferon-gamma production. These findings may help to elucidate the possibility of a rationally designed antihistamine strategy in melanoma therapy.

Animals↗
PubMed2002

Non-invasive measurement of biomechanical skin properties in systemic sclerosis.

OBJECTIVE: To evaluate biomechanical properties of skin in patients with systemic sclerosis (SSc) using the BTC-2000 suction device. METHODS: Twenty five patients with limited cutaneous SSc (lcSSc), 20 patients with diffuse disease (dcSSc), and 25 age matched healthy controls were evaluated. Viscoelastic deformation (VED, mm), elastic deformation (ED, mm), ultimate deformation (UD, mm), and pressure-deformation ratio (PDR, mm Hg/mm) were measured on the dorsal surface of the forearm, shoulder, and above the trapezius muscle on the back. RESULTS: Indices of skin extensibility (VED, ED, UD) were reduced and resistance to stress (PDR) increased in patients with dcSSc compared with healthy controls, or patients with lcSSc, at all three sites (p<0.001). At all sites, and overall, UD, ED, and VED were lower and PDR was higher at skin score above grade 2, compared with clinically normal skin. For both lcSSc and dcSSc biomechanical differences from controls were found even at sites of clinically normal skin. CONCLUSION: BTC-2000 is a sensitive tool for clinical evaluation of skin involvement in SSc and may be a valuable adjunct to skin sclerosis score in disease monitoring.

Adult↗
PubMed2002

[Specificity of inhibition between Salmonella strains].

A phenomenon of inhibition among Salmonella organisms colonizing the gut of young animals can be demonstrated which is important in connection with immunization using live Salmonella vaccines. For practical utilization of this inhibition phenomenon, research into its specificity is very important. In vitro broth culture and animal experiments have shown inhibition to be genus-specific, i.e. there is no inhibition between strains of different genera of Enterobacteriaceae in most cases. The strongest inhibition occurs between isogenic (identical genotype) strains (strain-specific inhibition). This applies to Salmonella and other genera of Enterobacteriaceae. There was a close correlation between the degree of the inhibitory effect and the genetic relatedness of the strains, as has been demonstrated in Salmonella strains of different epidemiological classification. The inhibitory capacity was most pronounced among closely related strains. Clonal strains of Salmonella Enteritidis phage type 4 fully inhibited caecal colonization by Salmonella Enteritidis phage type 4 strains in 65% of the combinations tested in chicks. In broth culture experiments, the share of combinations with complete inhibition was above 90%. A significant inhibitory competence of a selected strongly inhibitory Salmonella Enteritidis phage type 4 strain against the majority of Salmonella Enteritidis field isolates can be expected. However, Salmonella Enteritidis strains of all phase types showed almost no inhibitory competence against other Salmonella serotypes.

Animals↗
PubMed2001

Preparation, characterization, and luminescence properties of gallium-metal face-to-face diporphyrins (M = H(2), GaL, Ru(CO)(OH), Co).

The preparation and characterization of a new series of mixed metal cofacial anthracene-bridged diporphyrins (DPA) containing a GaL fragment (L = OMe, OH) and another metallic center (M = GaL, Ru(CO)(OH), Co, and H(2) (i.e. free base)) are reported. The luminescence properties at 298 and 77 K, in degassed EtOH solution, are also reported, and are characterized by a weak pipi fluorescence (2 < tau(F) < 7 ns) arising from the low energy Q-bands (S(1)-->S(0)). In the mixed diporphyrin systems, a strong pipi fluorescence is detected from the free base, while the transition metalloporphyrins of Co(II) and Ru(II) do not emit. The homobimetallic di[Ga(OMe)] species exhibits an unprecedented double (pi)(pi) fluorescence arising from the two lowest energy absorption Q-bands. On the basis of a comparison with photophysical data on GaL monoporphyrins, the weak fluorescence and absence of phosphorescence for most cases indicate efficient intramolecular quenching. To define structural features, the X-ray structures of (DPA)[Ga(OMe)](2) (2), (DPA)[Ga-(OH)-Ru(CO)] (5a), and (DPA)[Ga(OMe)-Ru(MeOH)(CO)] (5b) have been obtained. The structures of 5a and 5b demonstrate an interesting aspect of the structural chemistry of these ligands related to the internal methoxide and methanolic ligands in 5b (resulting in a large interplanar separation and center-to-center distance) and the internal metal-bridging hydroxyl ligand in 5a (resulting in a small interplanar separation and center-to-center distance). These data support previously reported discussions on the ability of the DPA and the DPB analogue (diporphyrinylbiphenylenyl) ligands to open and close their "bite" around the binding pocket between the porphyrin macrocycles.

Journal Article↗
PubMed2001

Relationship between posttranslational modification of transaldolase and catalase deficiency in UV-sensitive repair-deficient xeroderma pigmentosum fibroblasts and SV40-transformed human cells.

Xeroderma Pigmentosum (XP) is a rare recessively inherited human disease associated with a hypersensitivity to ultraviolet radiation. The ultraviolet component of sunlight can initiate and promote the formation of cutaneous tumors as seen in the skin cancer-prone XP patients. Previously, we have found that the low activity of the NADPH-dependent antioxydant enzyme, catalase, which we have observed in XP diploid fibroblasts and SV40-tranformed cells, could be restored by the addition of NADPH. Here we have analyzed transaldolase, which regulates NADPH levels produced by the pentose phosphate pathway in order to examine how it influences the catalase activity regulated in XP and SV40-transformed cells. We find that transaldolase activity is high in XP and SV40-transformed human fibroblasts, whereas transaldolase transcription is unchanged, suggesting that modification of transaldolase activity is due to a posttranslational modification of the protein. Two-dimensional electrophoresis analysis has allowed us to identify a complex set of transaldolase isoforms and to postulate that the phosphorylation of specific isoforms could be correlated with the different enzymatic activities seen. Our results show that high transaldolase activity corresponds to a low catalase activity in SV40-transformed cells and in fibroblasts from XP patients who have a high predisposition to develop skin cancer.

Acatalasia↗
PubMed2001

Founder BRCA1 and BRCA2 mutations in early-onset French Canadian breast cancer cases unselected for family history.

Recently, founder BRCA1 and BRCA2 mutations were identified in Canadian breast cancer and breast-ovarian cancer families of French ancestry. The presence of a breast cancer case diagnosed at younger than 36 years of age was strongly predictive of the presence of any founder mutation screened. Here we report the occurrence of founder BRCA1 and BRCA2 mutations in a series of 61 French Canadian women with invasive breast cancer diagnosed at age 40 or younger, unselected for family history of breast and ovarian cancer. Germline mutations in BRCA1 (n = 4) and BRCA2 (n = 4) were identified in 8 of 61 (13%) cases. All BRCA1 mutations were found in invasive ductal carcinomas, the most common histologic type of tumor in this series. In contrast, the BRCA2 mutations were found in tumors of various histologic types: two ductal carcinomas, a tumor containing both ductal and lobular histologic types and an invasive lobular carcinoma. Of the 37 women with at least one first-, second- or third-degree relative with breast or ovarian cancer and the 24 women with no history of these cancers, 7 (19%) and 1 (4%), respectively, were mutation carriers. The seven mutation carriers with a family history of cancer had at least one first-, second- or third-degree relative with a breast cancer diagnosis at less than 51 years of age. The identification of founder BRCA1 and BRCA2 mutations in young-onset breast cancer cases unselected for family history can facilitate carrier detection when the expected yield of a comprehensive screen may be low.

Adult↗