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Biomedical subjects

A Bernard

Publications and source records attributed to A Bernard.

At least 145 records · Page 8Linked to original sources
PubMed1998

Solitary plasmacytoma of the lung with light chain extracellular deposits: a case report and review of the literature.

AIMS: We present the clinical and histopathological findings of an unusual pulmonary plasmacytoma associated with light chain deposits. METHODS AND RESULTS: The tumour was located in the main left stem bronchus 40 mm from the carina. Histologically, it was composed of sheets of well differentiated plasma cells. Large extracellular deposits of amorphous material were observed in the tumour. These deposits were Congo red negative and contained kappa light chains. They were electron dense granular and non-filamentous. No plasmacytosis was identified by bone marrow biopsy and no monoclonal spike was shown by serum and urine electrophoresis. CONCLUSIONS: Our case is unusual in being endobronchial and showing light chain deposition.

Aged↗
PubMed1998

Characterization of a mouse serotonin 5-HT3 receptor purified from mammalian cells.

A serotonin 5-HT3 receptor was functionally expressed to high levels and on a large scale in mammalian cells with the Semliki Forest virus system. Conditions were optimized to maximize detergent solubilization of the receptor, while preserving ligand binding activity. An efficient one-step purification yielding approximately 50% of the histidine-tagged 5-HT3 receptor was achieved with immobilized metal ion chromatography. The expressed receptor, in both membranes and purified preparations, exhibited wild-type ligand binding properties, characterized by one class of binding sites. The purity of the receptor was shown by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, yielding a single band at 65 kDa, and was confirmed by the specific ligand binding activity of approximately 5 nmol/mg of protein. Deglycosylation of the receptor reduced the estimated relative molecular mass to 49 kDa. The apparent molecular mass of the functional receptor complex was determined by size exclusion chromatography to be 280 kDa, suggesting that the 5-HT3 receptor is a pentameric homooligomer. The secondary structure of the 5-HT3 receptor as determined by circular dichroism appeared to consist of mainly alpha-helices (50%) and beta-strands (24%), with minor contributions from nonregular structure (9%). The binding of either agonist or antagonist did not alter the secondary structure of the receptor.

Animals↗
PubMed1998

Sublethal alterations and sustained cell proliferation associated with the diethylstilbestrol-induced renal carcinogenesis in male Syrian golden hamsters.

The current study was initiated to explore the sublethal alterations and the tissue damage occurring in the hamster kidney during diethylstilbestrol-induced renal carcinogenesis. A total of 49 male Syrian golden hamsters (35 treated and 13 control animals) was utilized in the experimental procedure. Chronic exposure to diethylstilbestrol was achieved by s.c. insertion of implants containing 25 mg diethylstilbestrol. For long-term observation, adequate blood level of diethylstilbestrol was insured by renewing the implant every 2 months. Experimental groups (n = 4 to 9) were terminated 1, 2, 4, 6, 9 and 11 months after initial implantation for morphological examination of the kidney. Diethylstilbestrol carcinogenicity in this experimental model was confirmed by the observation that most animals undergoing drug exposure for 6 months or more exhibited renal neoplasms. The most striking nonneoplastic morphological abnormality disclosed by histological and cytological examination consisted in the accumulation of granular inclusions in proximal tubule cells. In renal tissue, the extent of cell proliferation determined by PCNA labeling progressively increased along with the duration of diethylstilbestrol exposure and suggested a sustained proliferative response in altered proximal tubules. The present data suggest that an impairment of functional tubular regeneration could promote, as well as the estrogen genotoxic effect, the tumorigenicity of diethylstilbestrol in the kidney of male hamsters.

Animals↗
PubMed1998

Intestinal infarctions: a reappraisal of the factors predictive of operative mortality.

OBJECTIVE: To assess the factors that predict operative mortality after intestinal infarction, and show what effect referral patterns have on mortality. DESIGN: Retrospective study. SETTING: Two university departments of surgery, France. SUBJECTS: 144 patients with intestinal infarctions operated on between January 1980 and August 1995. INTERVENTIONS: Univariate and multivariate analyses. MAIN OUTCOME MEASURES: Operative mortality and the factors associated with it. RESULTS: Operative mortality was 67% (96/144) during the first 45 days postoperatively. The univariate analysis showed that age over 75 years (p=0.0002), female sex (p=0.007), the presence of shock (p < 0.0001), and referral from cardiovascular medical or surgical unit (p=0.01) were significantly associated with mortality. However, the multivariate analysis reduced these to extent of infarction (p=0.0001), the presence of shock (p=0.0002), age over 75 years (p=0.0001), and recent cardiac or vascular operation (p=0.03). CONCLUSIONS: The influence of referral pattern was related to previous cardiac or vascular operation, and the risk among women to the fact that their age was 10 years older than that of men. This study shows how the type of referral may explain the wide variations in reported mortality. To compare published series, care should be taken to avoid any selection bias.

Adult↗
PubMed1998

Long-term adaptation to high-fat diets modifies the nature and output of postprandial intestinal lymph fatty acid in rats.

These studies were designed to investigate the lymph absorption of a lipid emulsion in rats prefed different long-term high-fat diets. Particular emphasis was placed on the consequences of endogenous fatty acid alteration on the lymph recovery of two labeled fatty acids. Male Wistar rats were fed a standard diet (LF) containing 3.5 g/100 g fat or high-fat diets containing 15 g/100 g sunflower oil (HSFO), menhaden oil (HMO) or medium-chain triglyceride oil (HMCT) for 4 wk. The lymph was collected for 3 h before and after the intraduodenal infusion of a 90 micromol lipid emulsion (30 micromol monopalmitin, 30 micromol oleic acid, 25 micromol linoleic acid, 5 micromol arachidonic acid) labeled with [3H] oleic (OA) and [14C] arachidonic (AA) acids. The [3H] OA and [14C] AA lymph recoveries were measured and the lymph samples were tested for fatty acid, phospholipid and triglyceride content. Prefeeding an HSFO or HMO diet led to a 65 or 32% greater total lymph fatty acid output, respectively, compared with rats prefed the LF diet. In rats prefed both the HSFO and HMO diets, lymph fatty acid characteristics provided evidence of a dilution of exogenous fatty acids coming from the emulsion by endogenous fatty acids. In rats prefed the HMCT diet, the total lymph fatty acid output after the infusion of the lipid emulsion was not greater than that of starved rats. Nevertheless, 27% [3H] OA and 21% [14C] AA were recovered in the lymph, suggesting a limited dilution of exogenous fatty acids by endogenous fatty acids. In rats prefed the HMCT diet, some exogenous long-chain fatty acids must have been transported by the portal vein in response to low biliary phopholipid production, as indicated by the proportions of [3H] OA and [14C] AA taken up by the mucosa and not recovered in the lymph. Thus we demonstrated that during absorption of a single long-chain fatty acid meal a dilution of exogenous fatty acids by endogenous fatty acids occurred. The nature and the quantity of these endogenous fatty acids could alter the absorption efficiency of long-chain fatty acids by the lymphatic pathway and modify the fatty acid characteristics of lymph lipoprotein.

Animals↗
PubMed1998

Adverse effects of chronic low level lead exposure on kidney function--a risk group study in children.

BACKGROUND: Children have been considered a risk group for lead (Pb) toxicity, mainly because of neurophysiological or neuro-cognitive deficits following Pb exposure. Blood Pb levels (b-Pb) of 100 microg/l currently have been defined as the lowest adverse effect level. The aim of this study was to compare, with the help of urinary markers, the kidney function of children with b-Pb just above this threshold with that of unexposed children, to assess from a nephrological point of view whether the current threshold is justified and whether children really are a particularly vulnerable risk group in terms of Pb-induced kidney damage. METHODS: In a cross-sectional study, 112 children, either from unexposed areas (controls, n=50) or Pb-contaminated areas (n=62), the latter partly with a known history of elevated b-Pb, were examined. Twenty nine urinary or serum markers mostly related to the function or integrity of specific nephron segments were determined (e.g. filtered plasma proteins, tubular enzymes, tubular antigens, eicosanoids). RESULTS: b-Pb were 39+/-13 microg/l in controls and 133+/-62 microg/l in exposed children. The main findings were increased excretion rates of prostaglandins and thromboxane B2, epidermal growth factor, beta2-microglobulin and Clara cell protein in the exposed children. A relationship between b-Pb and the prevalence of values above the upper reference limits was observed. CONCLUSIONS: With the help of urinary markers, nephron segment-specific effects of chronic low-level Pb exposure could be detected in children. The pattern of effects on glomerular, proximal and distal tubular and interstitial markers was similar to that previously observed in adults. The changes, however, occur at lower b-Pb levels than in adults. The current threshold appears to be justified also from a nephrological point of view, and children can indeed be considered a special risk group.

Biomarkers↗
PubMed1998

Clara cell protein (CC16) in pleural fluids: a marker of leakage through the visceral pleura.

Pleural fluid (PF) proteins either derive from serum by diffusion or are locally secreted within the pleural space. Another hypothetical origin is a leakage of lung secretory proteins across the visceral pleura. To test this hypothesis, we investigated the occurrence, sources, and determinants in PF of CC16, a small-size and readily diffusible protein of 16 kDa secreted by bronchiolar Clara cells. CC16 concentration was determined by a sensitive latex immunoassay in serum and PF of 117 subjects (86 exudates and 31 transudates) and, for purpose of comparison, in ascites samples from another group of 38 subjects (7 exudates and 31 transudates). CC16 was also studied in serum and PF of normal rats and in rats with pleural exudate induced by alpha-naphthyl-thiourea (ANTU). The levels of CC16 in PF and ascites were highly correlated with that in serum, suggesting a diffusional exchange across the pleural/blood and peritoneal/blood barriers. Whereas CC16 occurs at similar levels in ascites and serum, the protein was found to be more concentrated in PF than in serum in both humans (geometric mean in microg/L, 26.2 versus 14.6, p < 0.0001) and rats (213 versus 16.2, p < 0.001). A local synthesis of CC16 appeared unlikely in view of the lack of CC16-immunostaining in pleura of both species. The only plausible explanation for these findings is that CC16 in PF originates from two sources: diffusion from plasma and a leakage from the lung into the pleural space across the semipermeable visceral pleura. This interpretation is supported by a markedly increased leakage of CC16 in experimental exudates induced by ANTU and the finding of high CC16 concentrations in human transudates associated with congestive heart failure, two conditions wherein PF has been shown to arise from the interstitial spaces of the lung.

Aged↗
PubMed1998

Clearance of Clara cell secretory protein 16 (CC16) and surfactant proteins A and B from blood in acute respiratory failure.

Surfactant proteins A and B (SP-A and SP-B) enter the circulation in a manner that acutely reflects changes in pulmonary function in patients with acute respiratory failure (ARF). There is a small but significant gradient in SP-A and SP-B from arterial to mixed venous (A-V) blood, and since we have detected both proteins in urine, the kidney may be a major site of their systemic clearance. Clara cell secretory protein 16 (CC16), which leaks from the respiratory tract, is known to be freely eliminated by the kidney. Lung plasma protein levels will depend on the rates of both protein entry into and clearance from plasma. In order to study the limiting variable determining these levels, we compared plasma CC16, SP-A, and SP-B in matching A-V blood samples from 37 ARF patients with indices of lung dysfunction and glomerular filtration rate (GFR) (of plasma cystatin C and creatinine). Cystatin C, CC16, SP-A, and SP-B were reduced in mixed venous plasma (all p < 0.001) and their A-V gradients were directly related to their arterial levels (all p < 0.03). Whereas CC16, SP-A, and SP-B reflected blood oxygenation (all p < 0.05), only SP-A and SP-B were related to lung injury score (LIS) (both p < 0.05). In contrast, whereas the clearances of both CC16 and cystatin C were related to that of creatinine (p < 0.02 for both), the clearances of SP-A and SP-B were not. Our study confirms that all three lung proteins are acutely cleared from the circulation of patients with ARF (half-lives < 18 min), and we conclude that whereas the plasma concentration of CC16 depends on GFR, plasma concentrations of SP-A and SP-B reflect lung function independently of this variable.

Acute Disease↗
PubMed1998

Pneumoproteinaemia: a new perspective in the assessment of lung disorders.

Here we make the hypothesis that the determination of the concentration of lung specific secretory proteins in serum or pneumoproteinaemia could be used in the evaluation of lung disorders with a similar utility as proteinuria in kidney diseases involving the glomeruli. Human and experimental data indicate that comparable structural and functional features govern the passage of proteins across the lung epithelium/blood barrier and the glomerular filter. The concentrations in serum of some lung-specific secretory proteins, such as the bronchiolar Clara cell 16 kDa protein (CC16) and alveolar surfactant-associated proteins A and B (SP-A and SP-B, respectively), might be used to assess the integrity of the bronchoalveolar/blood barrier known to be disrupted in many lung disorders. In addition, if this barrier is intact or slightly compromised, these proteins might serve as peripheral markers to detect changes in secretory epithelial cells in the lung.

Biomarkers↗
PubMed1998

Testicular sperm aspiration (first Hungarian results).

Authors summarize the first results with the use of spermatozoas retrieved with direct surgical method in intracytoplasmic injection in Hungary (1995-1997). Eighty-nine procedures were performed in 65 patients and 84 cases were successful. Out of 84 cases 23 clinical pregnancies could be achieved (27.3%). Thirteen children were born, including one case of twins and one triplets.

Cytoplasm↗
PubMed1998

Activation of T cells via CD55: recruitment of early components of the CD3-TCR pathway is required for IL-2 secretion.

It was previously reported that the glycosylphosphatidylinositol (GPI)-anchored CD55 molecule provides a co-stimulatory signal for T lymphocytes and is constitutively associated with the Src-related kinase p56lck. The present studies were undertaken to clarify the mechanism of action of CD55 in T cells. We describe the failure of cross-linking of CD55 alone to induce both the elevation of the intracellular calcium concentration and the tyrosine phosphorylation of PLC-gamma in CD3+ Jurkat cells. By contrast, it is sufficient to induce the phosphorylation of tyrosine residues on p56lck, the TCR-zeta chain as well as ZAP-70. Surprisingly, the observed TCR-zeta and ZAP-70 tyrosine phosphorylations appear delayed compared to stimulation via CD3. Calcium ionophore A23187 in combination with cross-linked CD55 mAb initially caused an acceleration in the kinetic of these two phosphorylation events, followed by IL-2 secretion. Furthermore, transfection of the cytoplasmic domain of TCR-zeta in CD3- Jurkat cells, using a CD16-zeta chimera, demonstrates that CD55-mediated T-cell activation depends on the expression of this chain of the CD3-TCR complex.

Antibodies, Monoclonal↗
PubMed1998

Restrictions in the stem cell function of murine bone marrow grafts after ex vivo expansion of short-term repopulating progenitors.

We investigated the in vivo implications associated with the ex vivo expansion of 5-fluorouracil (5-FU) preactivated murine bone marrow (BM) grafts. Analysis of cultures established with BM cells collected 2 and 4 days after 5-FU treatment (2d and 4d 5-FU BM, respectively) and stimulated with IL-3 + IL-6 and IL-3 + SCF resulted in the generation of samples highly enriched for colony-forming units granulocyte/macrophage (CFU-GMs). This result was best shown in cultures established with 4d 5-FU BM and incubated for 3 days with IL-3 + SCF; in these samples up to 10% of the cellularity consisted of CFU-GMs. Analyses of the spleen colony-forming unit (CFU-S)12/CFU-S8 ratio revealed a continuous decline in this parameter during the expansion process, suggesting a predominant differentiation stimulus in the cultures. Transplantation of BM grafts into myeloablated recipients revealed a marked improvement in the short-term radioprotection capacity (30 days survival) of ex vivo expanded BM, which was most significant in the case of 3-day expanded grafts. In contrast to this finding, progressive impairment of the long-term radioprotection capacity of the grafts was found to be associated with the expansion process. Irrespective of the type of ex vivo manipulation used, a predominantly lymphohematopoietic repopulation by donor cells was observed in all recipients analyzed in the long term (4-7 months) posttransplantation. To investigate more thoroughly whether the repopulation ability of the grafts was modified to some extent during the ex vivo expansion process, BM competition assays were performed. The data obtained at 30 and 120 days posttransplantation indicated that under the best conditions assayed (4d 5-FU BM expanded for 3 days with IL-3 + SCF) almost no change in the competitive repopulation ability of the grafts was produced. However, when analysis was delayed to 300 days posttransplantation, a twofold reduction in the stem cell function of the expanded grafts was noted. Based on this data it is proposed that, under our experimental conditions, a significant expansion in the number of short-term repopulating progenitors is produced concomitantly with a differentiation stimulus of the culture, which moderately restricts the number and/or the longevity of the self-renewing stem cells.

Animals↗
PubMed1998

[The value of surgery in the treatment of invasive pulmonary aspergillosis in neutropenic patients].

The aim of the study is to specify the indication for surgery in the treatment of invasive pulmonary aspergillosis (API). From January 1991 to October 1996 nineteen patients who had been treated with chemotherapy and associated marrow aplasia and suffering from API were operated on. At the time of the surgical intervention all of the patients were treated with antifungal drugs. The delay between the start of their symptoms and the start of treatment was 2.6 days (range: 0-17 days). 1. The risk of a massive haemoptysis by contact between the fungal infection and the pulmonary artery led to eight urgent surgical operations: six lobectomies and two lobectomies associated with segmentectomy. The mean level of polymorphonuclear neutrophils was 296 cell/mm3 (0-1,000). Plastic surgery on the pulmonary artery was carried out in three patients. One patient died after the operation with progression of the API. The duration of postoperative stay was 13 days (6-18). 2. Planned surgery consisted of a resection of the residual mass after antifungal treatment and a diagnostic approach to the intraparenchymatous mass of indeterminate aetiology. A resection of the residual masses (in spite of antifungal treatment) was carried out in seven patients: before further haematological therapy in six cases and in one case for a superinfected lesion. The type of resection was: a lobectomy (n = 4), a lingulectomy (n = 1) and an atypical resection (n = 2). No postoperative deaths were reported. The patients left the surgical service between the seventh and twentieth day postoperatively. The surgery was used in four patients as the diagnostic approach in view of intraparenchymal masses of unknown aetiology and had enabled a fungal mycelium to be isolated at the centre of persisting inflammation. Antifungal treatment sometimes associated with surgery allowed for a better prognosis in patients suffering from invasive pulmonary aspergillosis.

Adolescent↗
PubMed1998

Serotoninergic control of the activity and expression of glial GABA transporters in the rat cerebellum.

Gamma-Aminobutyric acid (GABA) transporters (GAT-1, GAT-2, and GAT-3) play a key role in the termination of GABA transmission and the regulation of extracellular GABA concentrations. In the present study, pharmacological, cellular, and molecular analyses provide evidence for a modulatory effect of serotoninergic neurons on the activity and expression of glial GABA transporters in the rat cerebellum. Degeneration of serotoninergic neurons after in vivo 5,7-dihydroxytryptamine (5,7-DHT) treatment resulted in a significant decrease (-27%) in [3H]-GABA uptake into cerebellar punches. This decrease probably occurred via inhibition of GAT-2 or GAT-3 activity since their inhibitor, beta-alanine, induced a decrease in [3H]-GABA uptake in punches of sham-operated rats (-28%), but not in punches of 5,7-DHT-treated rats, demonstrating that serotonin terminal degeneration had already impaired the beta-alanine-sensitive component of GABA uptake. In contrast, nipecotic acid, a preferential inhibitor of GAT-1, induced comparable decreases in [3H]-GABA uptake comparable in punches of 5,7-DHT (-38%) versus sham-operated rats (-37%). The decreases in GAT-1 (-16%), GAT-2 (-34%), and GAT-3 (-32%) mRNA levels after 5,7-DHT treatment (detected by quantitative RT-PCR) are consistent with a serotoninergic control of GABA transporter expression at the transcriptional level. The cellular distribution of GAT-2 and GAT-3 mRNA, shown by in situ hybridization, suggests a glial localization of these transporters in the cerebellum and demonstrated a preferential anatomical localization of GAT-2 mRNA in the granular layer and of GAT-3 mRNA in the deep cerebellar nuclei. A direct serotoninergic control of glial GABA uptake was further demonstrated in vitro since serotonin stimulated the activity and mRNA expression of the GABA transporters in cerebellar astrocyte cultures.

5,7-Dihydroxytryptamine↗
PubMed1998

Quantification of Clara cell protein in rat and mouse biological fluids using a sensitive immunoassay.

Clara cell protein is a 16-17 kDa protein (CC16) secreted by Clara cells in the bronchiolar lining fluid of the lung. In order to investigate the potential of this protein as a pulmonary marker in animals, CC16 was isolated from rat bronchoalveolar lavage fluid (BALF) and a sensitive latex immunoassay applicable to both rat and mouse CC16 was developed. The pattern of CC16 concentrations in rat biological fluids determined by the immunoassay was consistent with the hypothesis of a passive diffusion of the protein across the bronchoalveolar/blood barriers showing a difference of more than 5,000 fold between the concentration in the epithelial lining fluid (mean, 140 mg x L(-1)) and that in serum (20 microg x L(-1)) or urine (3 microg x L(-1)). In BALF, the CC16 concentration averaged 5,500 microg x L(-1) and was of the same magnitude as that determined on lung and trachea homogenates. CC16 was also detectable in amniotic fluid with a mean value of 800 microg x L(-1) before delivery. Damage of Clara cells produced by methylcyclopentadienyl manganese tricarbonyl resulted in a significant decrease of CC16 in BALF but did not affect the serum levels of the protein. The nephrotoxicant sodium chromate by contrast had no influence on the CC16 content of BALF but markedly increased CC16 levels in both serum and urine as a result of impaired glomerular filtration and tubular reabsorption, respectively. In conclusion, mouse or rat Clara cell protein of 16-17 kDa can easily be quantified, not only in bronchoalveolar lavage fluid, but also in extrapulmonary fluids such as serum or urine. Thus, in rodents, Clara cell protein of 16-17 kDa follows the same metabolic pathway as in humans, diffusing from the respiratory tract into serum where it is eliminated by the kidneys. This serum Clara cell protein of 16-17 kDa may be useful as a peripheral marker of events taking place in the respiratory tract.

Animals↗
PubMed1998

[Hormonal replacement therapy and breast cancer].

Hormonal replacement therapy is prescribed more and more frequently to increase quality of life and decrease the symptomatic and organic consequences of the menopausal status. The different studies which analyzed the risk of breast cancer for women under hormonal replacement therapy show opposed conclusion. We reviewed articles published between 1980 and 1997 to try to conclude about the consequences of the action of this treatment in the risk of breast cancer from the characteristic of the hormonal replacement therapy and from known risk of breast cancer. Hormonal replacement therapy increases the incidence of breast cancer. Risk increase with the treatment duration and a low estrogen dose would be sufficient to palliate to the hormonal lack (< 0.625 mg/j). The risk of breast cancer becomes the same that this of women without hormonal replacement treatment when treatment interrupted. The association of estrogen and progestin should not be protective of breast cancer. But the hormonal treatment seems to be synergistic for the risk of breast cancer with late menopause, late age at the birth of first child. Hormonal treatment could increase the estrogenic period and should increased the risk of breast cancer in women with late age at menarche, late age at menopause and late age at first child. It should not increase the risk of breast cancer in women with benign breast disease, with family history of breast cancer and in nulliparous women. For women who undergone a bilateral oophorectomy before hormonal replacement treatment the risk would be the same than for women with natural menopause and without hormonal replacement treatment. However breast cancer should be diagnosed earlier in women with hormonal treatment because mammographies were made more frequently. Overall survival should not different between the women who were under hormonal therapy and theses were not.

Age Factors↗