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Biomedical subjects

D Simon

Publications and source records attributed to D Simon.

At least 217 records · Page 12Linked to original sources

Growth control and gene expression in a new hepatocellular carcinoma cell line, Hep40: inhibitory actions of vitamin K.

The growth characteristics of a newly established cell line, Hep40, derived from a human hepatoma are described. An absolute requirement was found for serum to mediate cell growth. Neither EGF, TGF-alpha, nor HGF altered cell growth in the presence or absence of serum. A partial suppression of cell growth was achieved by several TGF-beta family proteins. Affinity crosslinking gels using 125I-labeled TGF-beta showed a significant decrease in the TGF-beta cell-surface type II receptor in Hep40 cells, compared to the TGF-beta-sensitive Hep3B cell line. However, growth could be completely suppressed by addition of vitamins K to the culture medium in both Hep40 and several other hepatoma cell lines. Growth suppression by vitamins K was accompanied by an increased level of transcripts for c-myc, c-jun, and prothrombin genes, in contrast to the actions of TGF-beta 1 protein, which caused a decrease in the level of c-myc transcripts. These data show that this new human hepatoma cell line has partial resistance to growth inhibition by TGF-beta with a unique TGF-beta receptor defect. However, growth was completely suppressed by vitamins K. The differing gene expression patterns in response to TGF-beta as compared to vitamin K suggest that these two growth inhibitors act through differing pathways.

Animals↗

The "campus syndrome" in pigs: neurological, neurophysiological, and neuropharmacological characterization of a new genetic animal model of high-frequency tremor.

Inherited neurological diseases in animals are of interest to a wide range of scientific disciplines, particularly because such animals may be suited as genetic animal models for respective human disorders. Because the pig has a number of anatomic and physiologic features similar to those of human beings, this species is becoming increasingly popular in biomedical research. The usefulness of pigs as genetic models of neurological diseases is illustrated by the porcine model of malignant hyperthermia (MH), i.e., a frequently fatal myopathic disease in both pigs and humans. In the present study, we describe a new hereditary movement disorder in Pietrain pigs, which may represent a useful genetic animal model of high-frequency tremor. Because the disorder was first detected in the offspring of a boar named "Campus," we use the term "Campus syndrome" in this respect. Segregation analysis of breeding studies indicates that the syndrome is inherited as a monogenic dominant trait. DNA-based testing of the mutation involved in MH myopathy showed that expression of the Campus syndrome in pigs is not dependent on homozygosity for the MH mutation. In affected pigs, the Campus syndrome develops at an average age of 27 days. The syndrome is characterized by muscular weakness and a very intense tremor of the legs when standing and walking but not when at rest in a lying position. The intensity of tremor and muscular weakness progressively increases with age, resulting in pronounced postural instability. Despite these neurological abnormalities, body weight gain in affected pigs does not differ from that in unaffected siblings.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Population variation in migraine prevalence: a meta-analysis.

A meta-analysis of published studies was conducted to identify factors which explained variation in estimates of migraine prevalence. Twenty-four population based studies contributed a total of 168 gender and age specific estimates of migraine prevalence. In linear regression analysis, 70.6% of the variation in these prevalence estimates was explained by gender, age (AGE+AGE2), a binary variable for case definition, and an interaction term between age and the case definition. Initially, we identified five groups of case definitions among the 24 studies. Only the definition of Waters (any 2 of warning, nausea, or unilateral pain) was associated with statistically significant differences in prevalence estimates among studies; accordingly the other 4 groups were combined. Several other factors were examined as predictors of migraine prevalence including the method of selecting the study population, the source of the population, the response rate and whether diagnoses were confirmed by a clinical assessment. None of these factors substantially increased explained variance. We conclude that after taking sociodemographic factors and case definition into account, estimates of migraine prevalence are remarkably stable among studies.

Age Distribution↗

Molecular analysis of mutations in thyroid tumors with TGGE.

Immunohistochemical demonstration of overexpression of the p53 protein indicates a mutational alteration of the gene. Our own investigations of 59 differentiated thyroid carcinomas revealed an overexpression in 15% of the tumors. A correlation to unfavourable tumor prognosis was found (stage I and II: 0/11 (0%); stage III: 4/26 (14%); stage IV: 5/22 (23%)). For screening of one out of more than 300 possible mutations temperature gradient gel electrophoresis was employed. Analysis of the highly-conserved regions of the p53 gene (exon 5 to 8) could demonstrate a mutation in only 1 out of 31 differentiated thyroid carcinomas. The question arises whether accumulation of the protein is due to a mutational event or rather other molecular mechanisms.

Adenocarcinoma, Follicular↗

Experience with 500 extracorporeal shockwave lithotripsy patients using a low-cost unit: the "Econolith".

The Econolith (Medispec Ltd.) is a modular extracorporeal shockwave (SWL) system that uses the spark gap as its source for lithotripsy. In this study, the immediate and late results and complications in 500 patients (640 treatments) treated with this machine during the last 2 years were summarized. An average fragmentation rate of 86% was achieved after the first treatment. A stone-free situation at 3 months was achieved in 75% of the cases; 18% had small (< 5mm) fragments, and 7% had larger fragments. Auxiliary procedures were required in 8% of the patients. Minor complications such as hematuria, colic, and urinary tract infection were seen in 6% of the patients. The Econolith system is safe and effective. Its mobility and low cost enable any urologist to use this technology even with a low monthly turnover of patients.

Adolescent↗

Primary hyperparathyroidism: is technetium 99m-Sestamibi/iodine-123 subtraction scanning the best procedure to locate enlarged glands before surgery?

Technetium99m (99mTc)-Sestamibi/123I subtraction scanning was prospectively performed in 30 patients with primary hyperparathyroidism in an attempt to locate enlarged glands before first surgery. Imaging results were compared to surgical findings; the surgeon tried to identify all parathyroid glands. Twenty-seven patients were found to have a solitary adenoma during surgery, and 3 had multiglandular parathyroid hyperplasia. Twenty-six parathyroid adenomas (96%) were accurately located before surgery. The smallest gland detected weighted 125 mg. Preoperative detection of two mediastinal adenomas allowed them to be excised by median sternotomy during the initial operation. 99mTc-Sestamibi/123I subtraction scanning predicted multiglandular involvement in two patients with parathyroid hyperplasia, whereas it showed a solitary image in the third. Ten patients (33%) had associated nodular thyroid disease, hindering image analysis and leading to one false positive result. 99mTc-Sestamibi scanning seems to be better for locating enlarged parathyroid glands than other noninvasive imaging techniques. However, 1) difficulties associated with thyroid nodules call for complementary thyroid scanning; and 2) images showing a solitary enlarged parathyroid gland do not rule out multiglandular disease. This technique should help in detecting lesions, such as mediastinal glands, that are difficult to find at initial surgery.

Adult↗

Transient and restricted expression during mouse embryogenesis of Dll1, a murine gene closely related to Drosophila Delta.

The Drosophila Delta (Dl) gene is essential for cell-cell communication regulating the determination of various cell fates during development. Dl encodes a transmembrane protein, which contains tandem arrays of epidermal-growth-factor-like repeats in the extracellular domain and directly interacts with Notch, another transmembrane protein with similar structural features, in a ligand-receptor-like manner. Similarly, cell-cell interactions involving Delta-like and Notch-like proteins are required for cell fate determinations in C. elegans. Notch homologues were also isolated from several vertebrate species, suggesting that cell-to-cell signaling mediated by Delta- and Notch-like proteins could also underlie cell fate determination during vertebrate development. However, in vertebrates, no Delta homologues have yet been described. We have isolated a novel mouse gene, Dll1 (delta-like gene 1), which maps to the mouse t-complex and whose deduced amino acid sequence strongly suggests that Dll1 represents a mammalian gene closely related to Drosophila Delta. Dll1 is transiently expressed during gastrulation and early organogenesis, and in a tissue-restricted manner in adult animals. Between day 7 and 12.5 of development, expression was detected in the paraxial mesoderm, closely correlated with somitogenesis, and in subsets of cells in the nervous system. In adult animals, transcripts were detected in lung and heart. Dll1 expression in the paraxial mesoderm and nervous system is strikingly similar to the expression of mouse Notch1 during gastrulation and early organogenesis. The overlapping expression patterns of the Dll1 and Notch1 genes suggest that cells in these tissues can communicate by interaction of the Dll1 and Notch1 proteins. Our results support the idea that Delta- and Notch-like proteins are involved in cell-to-cell communication in mammalian embryos and suggest a role for these proteins in cellular interactions underlying somitogenesis and development of the nervous system.

Amino Acid Sequence↗

Leg ulcer odour detection identifies beta-haemolytic streptococcal infection.

beta-Haemolytic streptococci were identified in bacteriological cultures from 14 of 24 chronic venous leg ulcers in 21 patients. Multi-element odour detection (MEOD) analysis demonstrated a significant difference in odour in those ulcers from which beta-haemolytic streptococci were isolated (p < 0.01). MEOD has potential to detect pathogenic organisms instantaneously in the clinical setting.

Chronic Disease↗

Symptomatic fluid retention in patients on continuous peritoneal dialysis.

The clinical features, pathogenesis, management, prognosis, and predictors of symptomatic fluid gain (SFR) were analyzed for 71 episodes occurring in 66 patients on continuous peritoneal dialysis, 94.4% on continuous ambulatory peritoneal dialysis (CAPD) and 5.6% on continuous cycling peritoneal dialysis. Compared with a control group of 149 CAPD patients, the SFR group had a higher percentage of diabetics (64 versus 46%) and a higher frequency of noncompliance with fluid restriction (76 versus 22%), salt restriction (74 versus 23%), and performance of dialysis (30 versus 7%) (all at P < or = 0.015). Peripheral edema (100%), pulmonary congestion (80%), pleural effusions (76%), and systolic (83%) and diastolic (66%) hypertension were the most common manifestations of SFR. The annual hospitalization rate for SFR was 4.1 +/- 5.8 days per patient. SFR resulted in the discontinuation of CAPD in 10 patients and death in 1 patient. Serum sodium concentration was not different between dry and maximal weight in the SFR group. Thirty-eight (58%) of SFR and 61 (41%) of control patients were evaluated by peritoneal equilibration tests (PET). SFR patients had lower PET drain volume (2.08 +/- 0.47 versus 2.54 +/- 0.23 L) and a higher frequency of high peritoneal solute transport (32.2 versus 2.4%). In this group, logistic regression identified dietary noncompliance, low PET drain volume, and young age as independent predictors of SFR. Response to management and preventive measures was inconsistent. The best results were obtained by the use of short dwell exchanges with hypertonic dialysate in compliant patients with high peritoneal solute transport. SFR has serious consequences in CAPD. (ABSTRACT TRUNCATED AT 250 WORDS)

Diet, Sodium-Restricted↗

Integration of hepatitis B virus and alteration of the 1p36 region found in cancerous tissue of primary hepatocellular carcinoma with viral replication evidenced only in noncancerous, cirrhotic tissue.

We have studied the genetic profile of the host genome and hepatitis B virus (HBV) in HBV-associated primary hepatocellular carcinoma (HCC). Comparative analyses of HCC cell line Hep 40 and the original biopsy specimens showed the episomal and replicating form of HBV only in the biopsy specimen from nontumor (NT) cirrhotic liver tissue, where a molecular change in the 1p36 region was detected (NT tissue showed a normal 46XY karyotype). In contrast, only integrated HBV was detected in HCC tumor (T) tissue and Hep 40 cells. Two HBV integration sites were identical in HCC tissue and the hyperdiploid Hep 40 cell line, where genetic alteration in the 1p36 region was identified. These data indicate that viral replication is ongoing only in NT cirrhotic-hyperplastic, chromosomally normal tissue with evidence for genetic instability. Only the tumor cell with altered genotype has virus integrated

Carcinoma, Hepatocellular↗

[Current aspects of surgery of the parathyroid glands].

Diagnosis and treatment of primary hyperparathyroidism has changed substantially during recent years. Routine serum calcium measurements and development of specific as well as sensitive PTH assays made primary hyperparathyroidism the most prevalent diagnosis of hypercalcaemia in the normal population. With increasing numbers of asymptomatic patients secondary complications are reduced but the demands made on surgeon's technical skill are much higher. In view of our experience in 329 patients with primary hyperparathyroidism during the last six years and a success rate of 98% we refrain from any localisation technique and advocate visualisation of all four glands.

Adenoma↗

Late toxoplasmosis evidenced by PCR in a marrow transplant recipient.

We report a case of disseminated toxoplasmosis occurring 12 months after allogeneic BMT. The patient was seropositive for Toxoplasma gondii, and the donor was seronegative, so the patient was given anti-Toxoplasma prophylaxis. One year after BMT, he developed fever and muscle pain without other clinical symptoms. PCR amplification for T. gondii performed on blood was positive. Toxoplasma were found in bronchoalveolar lavage by PCR and in the marrow by special stains. With treatment, the PCR signal disappeared in 3 days while clinical symptoms resolved over 15 days. This case emphasizes the possibility of late toxoplasmosis after BMT despite prophylatic treatment, and the value of PCR in making the diagnosis.

Adult↗

Infectious colitides in patients with acquired immunodeficiency syndrome.

Diarrhea is a common problem in patients with acquired immunodeficiency syndrome (AIDS), and infections of the colon constitute a significant etiology. Cytomegalovirus (CMV) is the most common opportunistic infection of the colon in patients with AIDS, and it can involve any portion of the colon and the gastrointestinal tract. Because CMV is potentially treatable with either ganciclovir or foscarnet, it is important to evaluate endoscopically the entire colon of patients with AIDS with protracted diarrhea and no cause identifiable with routine stool and laboratory tests. In addition to CMV, there are a variety of other viral, bacterial, protozoal, and fungal infections seen in patients with AIDS. A thorough evaluation will help identify these pathogens, and those that are treatable can be given appropriate therapy.

AIDS-Related Opportunistic Infections↗

[Preventive radical surgery of C-cell carcinoma in MEN-II syndrome based on genetic screening].

Between April 1986 and July 1995 121 patients have been operated on for C-cell carcinoma with 70 (57.9%) patients presenting a sporadic type and 51 (42.1%) a hereditary type of disease (46/38% MEN IIa and 5/4.1% MEN IIb). Indication for operation in patients with familial disease (MEN II) was in 9 patients (18%) detection of a mutation in the ret protooncogen (group I), in 27 patients (53%) a pathologic biochemical screening (pentagastrin stimulation) (group II), and in 15 patients (29%) the first manifestation in a family (index) (group III). Distribution of stages showed a stage I (T1 N0 M0) in 8/9 (89%) in group I, in 17/27 (63%) in group II, and in 0/15 in group III. In 8 from 9 patients with genetic indication a multifocal microcarcinoma and in one patient a cell-cell hyperplasia could be demonstrated. Accordingly the rate of curative operations with postoperative normalization of basal and pentagastrin stimulated calcitonin levels was 100% (9/9) in group I, 59% (16/27) in group II, and 7% (1/15) in group III. The mean age was 14 (median 12) years in group I, 26 (median 24) years in group II, and 43 (median 40) years in group III). In patients with presymptomatic screening (genetic and biochemical) a thyroidectomy including lymph node dissection of the central compartment was performed as a standard procedure. Postoperative complication rate showed a recurrent nerve palsy of 0 in group I and 4% in group II and a hypoparathyroidism of 0 in group I and 4% in group II. The detection of a mutation correlated with positive histological findings of the disease in all patients. The prophylactic radical operation on the basis of a genetic screening proved to be a safe procedure with curative intention. The early age of manifestation underlines the importance of the genetic screening and the early indication for operation.

Adolescent↗

[Endonasal ethmoidectomy in naso-sinusal polyposis. Results in 110 surgically treated patients].

We assessed retrospectively functional and endoscopic results obtained in 110 patients who underwent endonasal ethmoidectomy (n = 218). The patients were divided into 3 groups according to associated pathology (polyposis alone, asthma without intolerance to aspirin, Widal's disease) and outcome was evaluated after a mean 19.5 month follow-up. Function was improved in 88% of the patients. Endoscopic recurrence was seen in 40% of the patients including 10% with major polyposis. Oedema of the mucose remained in 20% of the patients and the mucosa was normal in 40%. Improvement in patients with Widal's disease was the least favourable among the three groups and was best in those with asthma and no intolerance to aspirin. Post-operative complications occurred in 12.6% of the patients and were severe in 0.9%. These satisfactory results, both in terms of function and the low rate of complications, suggest that the current medicosurgical management should be continued with particular attention to the rate of endoscopic recurrence.

Adult↗