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Biomedical subjects

A Giraud

Publications and source records attributed to A Giraud.

At least 19 recordsLinked to original sources
PubMed2006

Aggressive fibromatosis--impact of prognostic variables on management.

OBJECTIVE: To determine the impact of prognostic variables on local control in patients with aggressive fibromatosis treated with or without radiation. MATERIALS AND METHODS: Forty-two patients presenting to the combined sarcoma clinic at Johannesburg Hospital with aggressive fibromatosis from 1990 to 2003 were analysed retrospectively. There were 14 males and 28 females. The lesions involved the head and neck in 6 cases (14%), the thorax in 6 (14%), the extremities in 19 (45%) and the abdomen in 11 (26%). Thirty-seven patients (88%) presented to the clinic for the first time, whereas 5 (12%) had recurrent disease at presentation. Fifteen patients (36%) underwent excision only, 15 (36%) had excision followed by postoperative radiation, 8 (19%) had biopsy only, and 4 (9%) had radiation only. The median dose of radiation was 60 Gy (range 9 - 70 Gy). RESULTS: One patient had local failure following excision and postoperative radiation therapy. The local control was 100% for surgery alone and 86% for surgery followed by postoperative radiation at > or = 24 months. On univariate analysis, age, sex, positive margins, primary or recurrent presentation, site of involvement and initial treatment did not affect local control significantly. Eight of 19 patients (42%) receiving radiation developed severe moist desquamation following treatment, and all these patients had doses of 60 Gy or more. CONCLUSION: Surgery with or without radiation therapy gave excellent local control. The addition of radiation therapy to surgery as well as other known prognostic parameters did not impact on local control. The morbidity of radiation treatment is considerable, as noted in this series, and adjuvant radiation therapy should therefore be considered only in situations where the risk of recurrence and the morbidity of re-excision are high.

Adolescent↗
PubMed2001

Hydrogen peroxide-induced production of a 40 kDa immunoreactive thyroglobulin fragment in human thyroid cells: the onset of thyroid autoimmunity?

We recently reported that, during in vitro thyroid-hormone synthesis, H(2)O(2) stress cleaved thyroglobulin (Tg) into C-terminal peptides. These peptides were found to contain the immunodominant region of Tg recognized by Tg autoantibodies from patients with an autoimmune thyroid disease. To test the hypothesis that Tg fragmentation is an early upstream initiating event involved in Tg autoimmune response and the consequence of oxidative injuries, we studied the effect of H(2)O(2) stress on human thyroid cells. In culture conditions allowing Tg synthesis and iodine organification by the cells, we found that bolus addition of increasing millimolar doses of H(2)O(2) induced a dose-response appearance of floating cells in the culture medium. These cells apparently resulted from a necrotic process, and they bore iodinated Tg fragments. These fragments were found to be similar to those previously obtained in vitro from purified Tg. In both cases, Tg peptides were recognized by a well-defined monoclonal antibody directed to the immunodominant region of Tg. The smallest immunoreactive Tg peptide had a molecular mass of 40 kDa and entered human thyrocytes more efficiently than the entire Tg. These data suggest that thyrocytes exposed to locally increased H(2)O(2) doses accumulate fragmented Tg for further delivery into surrounding living thyrocytes in the course of an autoimmune response.

Adenoma↗
PubMed2001

Costs and benefits of high mutation rates: adaptive evolution of bacteria in the mouse gut.

We have shown that bacterial mutation rates change during the experimental colonization of the mouse gut. A high mutation rate was initially beneficial because it allowed faster adaptation, but this benefit disappeared once adaptation was achieved. Mutator bacteria accumulated mutations that, although neutral in the mouse gut, are often deleterious in secondary environments. Consistently, the competitiveness of mutator bacteria is reduced during transmission to and re-colonization of similar hosts. The short-term advantages and long-term disadvantages of mutator bacteria could account for their frequency in nature.

Adaptation, Physiological↗
PubMed2001

Chemical nucleation for CVD diamond growth.

A new nucleation method to form diamond by chemically pretreating silicon (111) surfaces is reported. The nucleation consists of binding covalently 2,2-divinyladamantane molecules on the silicon substrate. Then low-pressure diamond growth was performed for 2 h via microwave plasma CVD in a tubular deposition system. The resulting diamond layers presented a good cristallinity and the Raman spectra showed a single very sharp peak at 1331 cm(-1), indicating high-quality diamonds.

Journal Article↗
PubMed2001

Role of complex asparagine-linked oligosaccharides in the expression of a functional thyrotropin receptor.

To evaluate the functional role of complex asparagine-linked oligosaccharides of the human thyrotropin receptor (TSHR), a Chinese hamster ovary cell line (JP09) and a K562 cell line (K562-TSHR) expressing this receptor were treated with deoxymannojirimycin (dMM), a mannosidase I inhibitor. dMM blocks the formation of complex-type structures and leads to the formation of high-mannose-type structures. Treatment of cells with dMM led to a decrease in the number of thyrotropin (TSH)-binding sites at the cell surface. Detection of the TSHR at the cell surface using a monoclonal antibody directed against the A subunit showed that this decrease was not due to a decrease in the number of TSHRs expressed at the cell surface. However the recognition of TSHR by a monoclonal antibody directed against the C peptide was greatly decreased. On immunoblotting, after deglycosylation using peptide N-glycanase F, the A subunit was visualized as a doublet (36 and 41 kDa). In control cells the species of higher molecular mass was more abundant whereas after dMM treatment the species of lower molecular mass became more abundant. This difference in molecular mass between the two peptides is compatible with the removal of the C peptide. In conclusion, the results show that inhibition of complex-type structure formation leads to (i) an incapacity for TSHR to bind TSH, without affecting its intracellular transport and (ii) an increase of TSHR susceptibility to proteases that remove the C peptide. We then hypothesized that removal of the C peptide could contribute to the formation of a non-functional TSHR.

1-Deoxynojirimycin↗
PubMed2001

The rise and fall of mutator bacteria.

Bacteria with elevated mutation rates are frequently found among natural isolates. This is probably because of their ability to generate genetic variability, the substrate for natural selection. However, such high mutation rates can lead to the loss of vital functions. The evolution of bacterial populations may happen through alternating periods of high and low mutation rates. The cost and benefits of high mutation rates in the course of bacterial adaptive evolution are reviewed.

Adaptation, Physiological↗
PubMed2001

Novel cis-acting replication element in the adeno-associated virus type 2 genome is involved in amplification of integrated rep-cap sequences.

This study identifies a region of the adeno-associated virus type 2 (AAV-2) rep gene (nucleotides 190 to 540 of wild-type AAV-2) as a cis-acting Rep-dependent element able to promote the replication of transiently transfected plasmids. This viral element is also shown to be involved in the amplification of integrated sequences in the presence of adenovirus and Rep proteins.

Base Sequence↗
PubMed2001

Identification of thyroglobulin domain(s) involved in cell-surface binding and endocytosis.

Thyroglobulin (Tg) binds to cell surfaces through various binding sites of high, moderate and low affinity. We have previously shown that binding with low to moderate affinity is pH dependent, selective, but not tissue specific. To identify the regions of Tg involved in this cell surface binding, we studied the binding of (125)I-labeled cyanogen bromide peptides from human Tg to cell surfaces of thyroid cells (inside-out follicles) and of CHO cells. Electrophoretic analysis of cell homogenates after binding of native or of reduced and alkylated (125)I-labeled peptides showed that three peptides, P1, P2 and P3, were always associated with the cells. Sequence analysis allowed the identification of P1 (Ser-2445 to Met-2596 or Met-2610) and P2 (Phe-2156 to Met-2306). P3 proved to be a mixture of several peptides among which two were identified: P3-1 (Cys-1306 to Met-1640) and P3-2 (Cys-2035 to Met-2413) which includes P2. P1, P2 and P3-2 are entirely (P1) or partly (P2 and P3-2) located in the C-terminal domain of Tg homologous with acetylcholinesterase. The smallest peptides, P1 and P2, were purified by preparative electrophoresis. They both displayed strong binding properties towards cell surfaces. Inhibition experiments of (125)I-labeled Tg binding by P1 or P2 indicated that they were involved in Tg binding to cell surfaces. All the other peptides tested for their binding abilities were either not or only poorly involved in Tg binding to cell surfaces, which suggested that P1 and P2 are major Tg sites of binding to cell surfaces. These two peptides are not involved in the binding of Tg to the known Tg 'receptors' described in the literature, to which recycling, transcytosis and regulation functions have been ascribed. Thus they are potential tools to identify cell surface components involved in the process of Tg endocytosis leading to lysosomal degradation.

Amino Acid Sequence↗
PubMed2000

Angiosarcomas--clinical profile, pathology and management.

Files of 8 patients with primary angiosarcomas treated in the Department of Radiation Oncology at the University of the Witwatersrand from 1982 to 1995 were identified. None of these patients had received prior radiotherapy or chemotherapy which would have predisposed them to the formation of an angiosarcoma. Slides of 6 patients were reviewed. Five of the 6 were confirmed as having angiosarcomas, while 1 patient was found to have a peripheral neuro-epithelial tumour. Four patients had angiosarcomas of the breast, while there was 1 patient each with angiosarcoma of the skin, intestine and brain. Complete excision was the primary modality of management whenever possible. Postoperative radiotherapy was given in cases of incomplete excision, patient refusal of radical surgery or gross tumour. Four patients died within 4 months of diagnosis. Three patients are alive (2 with no evidence of disease) 22-96 months after diagnosis. In 1 patient follow-up details were not available as he did not return for treatment. Angiosarcomas are aggressive malignant tumours arising from the endothelial cells. Complete surgical excision is the treatment of choice in the management of this aggressive disease, which has a poor prognosis.

Abdominal Neoplasms↗
PubMed1999

Generation of monoclonal antibodies to native human immunodeficiency virus type 1 envelope glycoprotein by immunization of mice with naked RNA.

The Semliki Forest virus (SFV) vector system is a new approach for in vivo expression of heterologous proteins and can also be used to generate specific immune responses in animal models. HIV-1 envelope glycoprotein produced using the SFV expression system is correctly folded, cleaved, transported to the cell surface and exhibits functional activity. We evaluated a recombinant Semliki Forest virus naked RNA-based immunization protocol for generation of monoclonal antibodies against the HIV-1 envelope glycoprotein. In vitro-transcribed RNA encoding for the SFV replicase complex and Env protein of HIV-1 (HXB2 strain) was injected intramuscularly to mice. This approach elicited an Env-specific antibody response in four mice out of five and a monoclonal antibody, 12H2, directed against gp41 was produced. Our results show that recombinant SFV RNA immunization can potentially be used as a quick and direct method to produce monoclonal antibodies, with the particular advantage that vectored RNA, rather than purified antigen, delivers a complex oligomer produced correctly.

Animals↗
PubMed1998

Comparison of concentrations of sulbactam-ampicillin administered by bolus injections or bolus plus continuous infusion in tissues of patients undergoing colorectal surgery.

The concentrations of sulbactam and ampicillin were determined in sera and different abdominal tissues of 16 patients who underwent elective colorectal surgery. Patients were randomly allocated to two groups. At the time of induction of anesthesia, patients in group 1 (eight patients) were given 1,000 mg of sulbactam with 2,000 mg of ampicillin by intravenous bolus injection (3 min). This dose was administered again after 2 h by bolus injection by the same route. Patients in group 2 (eight patients) were given the same initial dose of sulbactam-ampicillin by bolus injection (3 min). Then, a continuous infusion of 1,000 mg of sulbactam with 2,000 mg of ampicillin in normal saline was immediately started and was administered over a 4-h period. Blood samples were collected to determine peak (10 min) and trough (end of surgery) antibiotic levels. Serial blood samples were also collected at predetermined periods (at the time of opening and closing of the abdominal cavity and at the time of surgical anastomosis). Abdominal wall fat, epiploic fat, and colonic wall tissue samples were collected simultaneously. Antibiotic concentrations were determined by high-performance liquid chromatography. Similar levels of the drugs in serum were observed for the two regimens of administration, with trough sulbactam levels of 33 +/- 16 and 37 +/- 22 microg/ml in groups 1 and 2, respectively, and trough ampicillin levels of 72 +/- 55 and 79 +/- 47 microg/ml in groups 1 and 2, respectively. Similar sulbactam concentrations were observed in abdominal tissues whichever regimen of administration was used; in fatty tissues the sulbactam concentrations ranged from 2.7 to 3.8 microg/g for group 1 and from 1.7 to 4.0 microg/g for group 2, and sulbactam concentrations in the colonic wall were 5.6 +/- 7.7 and 6.8 +/- 3.2 microg/g in groups 1 and 2, respectively (not significant). Again, no influence of the regimen of administration was observed on tissue ampicillin concentrations; in fatty tissues ampicillin concentrations ranged from 4.1 to 5.4 microg/g for group 1 and from 3.2 to 5.8 microg/g for group 2, and sulbactam concentrations in the colonic wall were 7.0 +/- 2.8 and 11.0 +/- 4.7 microg/g for groups 1 and 2, respectively (not significant). In most patients, the concentrations of ampicillin-sulbactam were greater than the MIC at which 50% of isolates are inhibited (MIC50) for Bacteroides fragilis in the fatty tissues. In the colonic wall, for most patients the concentrations of ampicillin-sulbactam were greater than the MIC90 for B. fragilis. No influence of the regimen of administration was observed on the ratio of the two components in the tissues investigated and in sera. In conclusion, a second intraoperative bolus injection or a continuous infusion were equally effective in maintaining sulbactam-ampicillin concentrations in abdominal tissues. The first method of administration can be recommended since it is easier to handle.

Ampicillin↗
PubMed1998

Outpatient care in emergency departments: feasibility and comparison of three strategies for follow-up.

The outpatient population using the emergency department (ED) is increasing and so is the risk of not admitting people who need it. There is, thus, one important question: are the services delivered appropriate to the needs of these ED outpatients? Follow-up of non-admitted patients after a visit to the ED is a prerequisite for the evaluation of these health services. A multicentric follow-up study was thus performed in order to assess the possibility of contacting outpatients after a visit to the ED. Three randomized follow-up methods were compared: (1) telephone call 1 week after the emergency department visit; (2) telephone call 2 weeks after the visit; (3) telephone call 4 weeks after the visit. The follow-up rate did not change depending on whether patients were contacted at 1, 2 or 4 weeks after the visit. The success rate was 78.6%, 85.6% and 74% respectively (NS). In each strategy, 50% of patients were contacted at the first telephone call, 20% at the second telephone call and 10% by mail. Thus, in a group of outpatients who gave their consent to be called, the follow-up was found to be feasible with a high success rate whatever the time between the visit and the phone recall.

Adolescent↗
PubMed1998

[Networks of care and diabetes: an obvious need].

In 1958, the French Government issued ordinances that profoundly reformed medical education and hospital practice. Hospital physicians in the public sector became full-time state employees and could no longer conduct private practice in town. By creating a prestigious and powerful public hospital sector, the 1958 ordinances set the stage for the significant developments that French academic medicine and medical research have experienced since then. However, they also created a gap between the hospital and medicine community. In this way, many patients with chronic diseases such as diabetes followed on a routine basis by their family practitioner may need periodic hospital evaluation and thus discover that their care lacks continuity and therefore quality. The 1996 ordinances, by instituting experimental integrated care networks, have tried to remedy this structural defect in the French health care system. Such networks seem particularly well-suited for diabetic patients.

Community Networks↗
PubMed1997

Binding and internalization of thyroglobulin: selectivity, pH dependence, and lack of tissue specificity.

Thyroglobulin (Tg), the precursor of thyroid hormones, follows a unique secretion, storage, and recapture pathway. The first steps of recapture were studied by investigating the binding of 125I-labeled Tg on the apical surface of inside-out follicles and its internalization. The selectivity of the process was assessed by using molecules other than Tg and/or nonthyroid cells. Tg binding to the apical surface of thyroid inside-out follicles is selective relative to the binding of other molecules. It increases sharply over pH 8.0 and occurs through specific sites of moderately high affinity (Kd = approximately 200 nM; 2 x 10(4) sites/cells). At pH < 8.0 it occurs through numerous sites of very low affinity considered nonspecific. Endocytosis, although weak under our conditions, increases at pH 8.0 concomitantly with binding. Over pH 8.2, however, some inhibition occurs. Surprisingly, Tg binding and endocytosis are not tissue specific, as they showed the same properties on thyroid inside-out follicles and Madin-Darby canine kidney or Chinese hamster ovary cells. Thus, a selective uptake of Tg mediates its recapture by thyroid cells. This selectivity is an intrinsic Tg property, not dependent on the thyrocyte apical surface, as it was observed with Madin-Darby canine kidney and Chinese hamster ovary cells. Given the pH effect observed, we suggest that Tg binding is a regulated phenomenon and that, through luminal pH control, it can vary from a basal level at neutral pH to a stimulated level over pH 8.0.

Animals↗
PubMed1997

Symmetrical multifocal liposarcoma.

Multiple liposarcomas are extremely rare. We report on a patient with liposarcoma of the right lower limb who had undergone surgery and radiotherapy 4 years previously for a liposarcoma in the left lower limb. An outline of the management is discussed and a short review of available literature is given.

Humans↗