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Biomedical subjects

C Guerin

Publications and source records attributed to C Guerin.

At least 19 recordsLinked to original sources

Selective endothelial growth inhibition by tetracyclines that inhibit collagenase.

The potential of angiogenesis inhibitors as therapy for human diseases is limited by a lack of clinically available agents. We investigated the mechanism of the anti-angiogenesis effects of minocycline, a commonly used drug, and several derivatives. Endothelial cell proliferation was inhibited by several of these compounds. We found that inhibition was associated with inhibition of collagenase, did not require antibiotic activity, and was not related to cytotoxicity. Other microvessel-associated cells were unaffected. This endothelial antiproliferative effect is a potential mechanism of the anti-angiogenic activity of minocycline.

Animals

Sarcoplasmic-reticulum biogenesis in contraction-inhibited skeletal-muscle cultures.

We have previously shown that inhibition of the spontaneous contractile activity of cultured embryonic-chick skeletal-muscle fibres with tetrodotoxin (TTX) leads to decreased sarcoplasmic-reticulum Ca(2+)-transport rates and steady-state concentrations of the high-energy Ca(2+)-ATPase phosphoenzyme intermediate [Charuk & Holland (1983) Exp. Cell Res. 144, 143-157]. In the present study we used a monoclonal antibody to the Ca(2+)-ATPase to show that there is a decreased amount of enzyme accumulated by contraction-inhibited myotubes. Indirect immunofluorescence microscopy using the monoclonal antibody to the Ca(2+)-ATPase also revealed a disordered subcellular organization of the sarcotubular system in contraction-inhibited myotubes. The biogenesis of sarcoplasmic-reticulum proteins in TTX-paralysed myofibres was studied by labelling cells with [35S]methionine before isolation of the active Ca(2+)-pump membrane fraction. Protein turnover was selectively increased in that fraction from TTX-treated muscle cultures. Electrophoretic analysis and quantitative fluorography confirmed that decreased accumulation of the Ca(2+)-ATPase enzyme in contraction-inhibited myotubes was associated with increased turnover of this protein. The present results demonstrate that biogenesis of the sarcoplasmic-reticulum Ca(2+)-ATPase is regulated by the contractile activity of skeletal-muscle fibres.

Animals

Vascular differentiation and glucose transporter expression in rat gliomas: effects of steroids.

The GLUT1 isoform of the glucose transporter is normally expressed at high levels in differentiated brain vessels that also express a permeability barrier. In contrast, malignant brain neoplasms have relatively undifferentiated vessels that are highly permeable, proliferate to high vascular densities, and often lose GLUT1 expression. Using the rat intracerebral 9L glioma model, we investigated whether dexamethasone-induced changes in permeability are associated with the appearance of other differentiated vascular properties. The percentage of vessels expressing immunohistochemically detectable GLUT1 (74.2 +/- 6.1%) and the tumor vessel density as assessed by laminin immunostaining (282 +/- 37 vessels/mm2) did not vary with control tumor size. Dexamethasone treatment resulted in an 83% reduction of vascular permeability to intravenous Evans blue, an increased percentage of vessels expressing GLUT1 (106.4 +/- 10.5%), lower vascular density (102 +/- 64 vessels/mm2), and smaller tumor size (control cross-sectional area, 17.0 +/- 3.4 mm2; treated, 4.6 +/- 1.0 mm2). Essentially all vessels became GLUT1-positive after dexamethasone treatment. Increased GLUT1 expression by glioma vessels in association with the appearance of other signs of differentiation (low vascular density, slow tumor growth) suggests that immunostaining for GLUT1 may identify neoplasms that are biologically less aggressive.

Animals

Prevention of nosocomial pneumonia in intubated patients: respective role of mechanical subglottic secretions drainage and stress ulcer prophylaxis.

Chronic microaspiration through a tracheal cuff is the main culprit in the penetration and colonization of the lower respiratory tract. A total of 145 patients intubated for more than 3 days were randomly assigned to a double nosocomial pneumonia (NP) prevention: 1--Prevention of aspiration by hourly subglottic secretion drainage (SSD) with a specific endotracheal tube (HI-LO Evac tube, Mallinckrodt); 2--Prevention of gastric colonization using either sucralfate or antacids. Four random groups were defined, similar in age and severity of illness. Subglottic secretion drainage treatment was associated with: a) a twice lower incidence of NP (no-SSD: 29.1%, SSD: 13%); b) a prolonged time of onset of NP (no-SSD: 8.3 +/- 5 days, SSD: 16.2 +/- 11 days); c) a decrease in the colonization rate from admission to end-point day in tracheal aspirates (no-SSD: +21.3%, SSD: +6.6%) and in subglottic secretions (no-SSD: +33.4%, SSD: +2.1%). Sucralfate was not associated with a significantly lower incidence of NP (antacids: 23.6%, sucralfate: 17.8%), but with a lower increase in the colonization rate in subglottic and gastric aspirates, from admission to end-point day.

Adult

Vascular expression of glucose transporter in experimental brain neoplasms.

Vascular abnormalities in brain neoplasms are important to tumor biology and therapy. Glucose transporter (GLUT1) expression is a differentiated property of normal cerebral microvessels typically associated with expression of the blood-brain barrier. We investigated the relationship of GLUT1 expression to other vascular characteristics in F98, 9L, and C6 gliomas and Walker 256 carcinomas implanted into adult rat brains. The percentages of microvessels with immunohistochemically detectable GLUT1 were 95.5 +/- 3.9 in F98, 60.9 +/- 3.9 in 9L, 45.4 +/- 5.6 in C6, and 1.2 +/- 0.3 in Walker 256 (mean +/- SEM). The percentage of GLUT1-positive vessels in F98 was not statistically different from that in normal brain. GLUT1 expression was not dependent on restricted permeability as all tumors were highly permeable to Evans blue. GLUT1 expression was unrelated to vascular density, vascular morphology, and parenchymal GFAP expression. The expression of GLUT1, a marker of cerebral endothelial differentiation, is a newly described property of glial tumor vessels that may have diagnostic and prognostic significance.

Animals

Prognostic factors in mesangial IgA glomerulonephritis: an extensive study with univariate and multivariate analyses.

To clarify the risk factors for chronic renal failure in idiopathic IgA glomerulonephritis (IgA-GN), we performed a dual study on 282 patients using both standard univariate statistical methods and the multivariate regression model of Cox. During a follow-up ranging from 1 to 36 years, with a mean of 8 years, 18% of the patients (50/282) had gone into chronic renal failure (CRF), with 18 of them in end-stage renal disease (ESRD) (6%). The univariate comparison of patients with CRF versus patients without CRF showed multiple risk factors: mainly arterial hypertension, an amount of proteinuria, nephrotic syndrome, a high level of serum IgA, presence of HLA-B35 antigen, and the intensity of most pathological lesions on light microscopy. The actuarial survival rate for a normal renal function (serum creatinine less than 135 mumol/L [1.5 mg/dL]) was 84% at 10 years and 64% at 20 years. The multivariate study allowed the isolation of only four risk factors with a significant effect on survival rate. These were the amount of proteinuria, the global optical score on first renal biopsy, the presence of an initial hypertension, and the presence of the HLA-B35 antigen. From these results, the probability of renal survival for individual patients may be calculated and a high-risk subgroup defined. Our data confirm the greater usefulness of multivariate over univariate statistical analyses in finding risk factors for CRF in IgA-GN.

Adolescent

Renal transplantation with a current T negative but historical T and/or B positive cross-match.

We report our experience of 36 renal transplanted patients against a current T negative allo-cross-match, but historical T and/or B positive allo-cross-matches, whatever the result of the current B cross-match. Additionally, we have determined the immunoglobulin class of the antibody directed against B and T lymphocytes. The graft survival rate did not differ between the 36 patients forming the study group, and the 229 patients transplanted within the same period with negative T and B, on current and historical sera, cross-matches. Within this study group there was no changes in graft survival rate for the following three subgroups, which were retrospectively defined: historical positive (14 patients) versus negative (22 patients) T cross-match, current positive (15 patients) versus negative (21 patients) B cross-match, and IgM (16 patients) versus IgG (20 patients) against B lymphocytes. In terms of transplant outcome, our policy was thus safe.

Adult

The glucose transporter and blood-brain barrier of human brain tumors.

The glucose transporter of the human brain has been localized to endothelial cells expressing the blood-brain barrier, but little is known regarding its mechanism of induction or whether its expression is exclusively linked with restricted vascular permeability. We investigated glucose transporter expression by vessels in human astrocytic tumors and pulmonary metastases to the brain using immunohistochemical techniques. Vessels in 9 of 10 low-grade astrocytomas and 8 of 10 anaplastic astrocytomas were positive for glucose transporter. Glioblastoma vessels were transporter-positive in only 2 of 10 specimens. Vessels in all three metastatic tumors were negative for the glucose transporter. The decrease in transporter expression observed in higher-grade tumors occurred independently of increases in vascular permeability. In low-grade astrocytomas and glioblastomas transporter expression and contrast enhancement were inversely related, but vessels in 6 of 9 anaplastic astrocytomas were transporter-positive despite contrast enhancement. These findings suggest that separate mechanisms induce the glucose transporter and the permeability restrictions of the human blood-brain barrier. They also have potential implications for the therapy and prognosis of astroglial neoplasms.

Adult

Astrocytes induce neural microvascular endothelial cells to form capillary-like structures in vitro.

Astrocytes maintain a unique association with the central nervous system microvasculature and are thought to play a role in neural microvessel formation and differentiation. We investigated the influence of astroglial cells on neural microvascular endothelial differentiation in vitro. Using an astroglial-endothelial coculture system, rat brain astrocytes and C6 cells of astroglial lineage are shown to induce bovine retinal microvascular endothelial (BRE) cells to form capillary-like structures. Light microscopic evidence for endothelial reorganization began within 48 hours and was complete 72-96 hours following the addition of BRE cells to 1-day-old astroglial cultures. The extent of BRE reorganization was quantitated by computer-assisted analysis and shown to be dependent upon the density of both the BRE and C6 cells within the cocultures. Coculture conditions in which BRE cells were separated from C6 cells by porous membranes failed to generate this endothelial cell change. Likewise, C6-conditioned media and C6-endothelial coculture conditioned media did not induce BRE cell reorganization. Extracellular laminin within the C6-endothelial cocultures, identified by indirect immunofluorescence, was concentrated at the endothelial-astroglial interface of capillary-like structures consistent with incipient basement membrane formation. Astroglial cells accumulated adjacent to capillary-like structures suggesting the presence of bidirectional influences between the reorganized endothelial cells and astroglia. This is the first demonstration of astroglial induction of angiogenesis in vitro and these findings support a functional role for perivascular astrocytes in the vascularization of neural tissue such as retina and brain.

Animals

[Urinary fistula after renal transplantation].

Among 336 consecutive renal transplantations performed in our centre from March 1979 to December 1988, we have observed 26 cases of urinary leak in 25 patients. We have separated the ischemic and non-ischemic urinary leaks. The former (11 episodes) would have been prevented in most cases with better graft removal. The latter (15 episodes) were predominantly secondary to an anastomotic leak. We have treated surgically these urological complications. Only one patient died. The one-year graft survival rate was 67% in the 25 kidneys but the graft loss was directly due to the urinary leak in three cases.

Actuarial Analysis

Inflammatory intracranial mass lesion: an unusual complication resulting from the use of Gelfoam.

There are few reported complications associated with the use of Gelfoam. We report the case of a 29-year-old woman who developed signs and symptoms of meningeal inflammation and an expanding intracranial mass related to the intracranial use of Gelfoam. Findings were confirmed by surgical exploration. Signs and symptoms resolved promptly after therapy with intravenous dexamethasone, but complete resolution of radiological findings required 5 months. As the use of Gelfoam is essential to neurosurgical practice, it is important to be aware of significant complications related to its use.

Adult

[Monitoring of renal grafts. Value of the determination of serum neopterin and neopterin versus creatinine ratio].

In a longitudinal study, 53 renal allograft recipients were investigated for changes in serum creatinine and neopterin levels and in the neopterin/creatinine (N/C) ratio which makes it possible to disregard the glomerular filtration level. The patients were divided into 5 groups according to their clinical situation: stability, acute renal failure due to acute tubular necrosis, acute graft rejection, bacterial or viral infection and cyclosporin overdosage. Only N/C discriminated between these situations, being normal (less than 200.10(-6) in groups 1 and 2, significantly elevated in groups 3 and 4 and low in group 5. The highest N/C value was observed in patients with primary cytomegalovirus infection. It is concluded that the N/C ratio is a good biochemical parameter to be used in the follow-up of renal allograft recipients.

Adult