Biomedical subjects

A Serban

Publications and source records attributed to A Serban.

At least 19 recordsLinked to original sources

PubMed2005

[Primary meningeal intermediate grade melanocytic neoplasm: case report with radiologic-pathologic correlation].

A case of primary meningeal intermediate grade melanocytic neoplasm involving the right C2 nerve root is presented. MRI findings may suggest this rare entity, especially when an extra-axial lesion is located in the posterior fossa or cervical spinal canal and demonstrates shortening of both T1 and T2. Eventually, definitive diagnosis relies on histology which demonstrates spindle-shaped melanocytic cells that are Fontana stained and positive for HMB:45 antigen. Cellularity, pleomorphism, mitotic rate, proliferation index and invasiveness are useful criteria to distinguish among the spectrum of primary melanocytic tumors of the central nervous system ranging from melanocytoma to malignant melanoma.

Adult↗

PubMed2003

[Management of childhood obesity].

The prevalence of obesity is currently increasing in children and young adolescents in France, and affects about 10 to 14% of them. Therapeutic objectives should aim to improve, on the long-term, the weight/body mass index curve. Restrictive diet and weight loss should not be the primary target. The focus has to be on a balanced healthy diet, tailored to children growth, associated with a regular physical activity. Children weight management should be within the usual life conditions, taking into account familial and social environmental conditions, through a multidisciplinary team approach as those implemented in our paediatric medical centre. The objectives, management steps and current results of our therapeutic educational project are described.

Adolescent↗

PubMed2001

Immobilized prion protein undergoes spontaneous rearrangement to a conformation having features in common with the infectious form.

It is hypothesized that infectious prions are generated as the cellular form of the prion protein (PrP(C)) undergoes pronounced conformational change under the direction of an infectious PrP(Sc) template. Conversion to the infectious conformer is particularly associated with major structural rearrangement in the central portion of the protein (residues 90-120), which has an extended flexible structure in the PrP(C) isoform. Using a panel of recombinant antibodies reactive with different parts of PrP, we show that equivalent major structural rearrangements occur spontaneously in this region of PrP immobilized on a surface. In contrast, regions more towards the termini of the protein remain relatively unaltered. The rearrangements occur even under conditions where individual PrP molecules should not contact one another. The propensity of specific unstructured regions of PrP to spontaneously undergo large and potentially deleterious conformational changes may have important implications for prion biology.

Animals↗

PubMed2000

Evolution of GH secretion in urine during an in-patient slimming course in obese children.

OBJECTIVE: To estimate the change in GH excretion in urine (GH-U) during a slimming course, and if increased, to assess the components of the course related to the increase in obese children. DESIGN: Observational follow-up study of patients admitted for primary obesity to an in-patient slimming course lasting at least 10 weeks. SUBJECTS: 48 complete observations out of 54 consecutive pre-pubertal patients admitted to a paediatric centre for treatment of primary obesity (BMI greater than the 90th percentile of the national reference curves). MEASUREMENTS: GH excretion in urine by immunoradiometric assay, at entry and after 10 weeks, various anthropometric measurements, nutritional intake and departure from the prescribed diet, time spent in physical activity, sleep duration. RESULTS: A mean decrease of 0.90 standard deviations for BMI was accompanied by a 34% increase of GH-U. Time spent in physical activity was the only component of the course found to be related to the magnitude of GH-U increase. CONCLUSION: The results of this observational study confirm that GH-U is increased after a slimming course in children, and suggest that physical activity is a major contributor to the restoration of normal GH-U levels.

Body Constitution↗

PubMed1998

Dual energy X-ray absorptiometry of the hand and wrist--a possible technique to assess skeletal maturation: methodology and data in normal youths.

Ninety five normal Caucasian subjects (51F, 44M) aged from 2 to 25 y were measured at the hand and wrist level with a small DXA system (pDEXA) in order to obtain the normal values of the bone mineral content (BMC), density (BMD) and projected area (A) of carpal (c) and metacarpal (m) bones. BMDc ranged from 0.065 +/- 0.007 g/cm2 to 0.365 +/- 0.035 g/cm2 in females and 0.425 +/- 0.040 g/cm2 in males. It presented a sharp change of increase rate at 15.5 and 17 y of age in girls and boys, respectively. Ac presented the same kind of evolution as BMDc, but had a larger value dispersion. The second metacarpal bone had the highest BMCm value in 85% of females and 90% of males. The sum of BMCmi or Ami values (i = 1-5) and the projected mean density of the 5 metacarpal bones was well correlated with BMCc, Ac and BMDc, respectively (r > 0.90). A volumetric mineral density, dmi, calculated for each of these bones, approximated to a cylinder, was correlated with age (r > 0.85).

Absorptiometry, Photon↗

PubMed1996

Nonclassical adrenal hyperplasia due to 21-hydroxylase-deficiency: does genotyping predict the clinical manifestation?

8 patients of 7 families with nonclassical adrenal hyperplasia (NCAH) were analysed for defects of the 21-hydroxylase-B-gene. As the defects were small or rare, complete molecular genetic diagnostic up to sequencing of this gene was necessary to detect the genotype, which then was associated with the phenotype. However, mutations in 4 alleles from 3 families are still undetectable. Thus, correct prenatal diagnosis in NCAH-families without index patient remains difficult.

Adolescent↗

PubMed1994

Spectroscopic characterization of conformational differences between PrPC and PrPSc: an alpha-helix to beta-sheet transition.

Although no chemical modifications have been found to distinguish the cellular prion protein PrPC from its infectious analogue PrPSc, spectroscopic methods such as Fourier transform infrared (FTIR) spectroscopy reveal a major conformational difference. PrPC is rich in alpha-helix but is devoid of beta-sheet, whereas PrPSc is high in beta-sheet. N-terminal truncation of PrPSc by limited proteolysis does not destroy infectivity but it increases the beta-sheet content and shifts the FTIR absorption to lower frequencies, typical of the cross beta-pleated sheets of amyloids. Thus the formation of PrPSc from PrPC involves a conformational transition in which one or more alpha-helical regions of the protein is converted to beta-sheet. This transition is mimicked by synthetic peptides, allowing predictions of domains of PrP involved in prion diseases.

Amino Acid Sequence↗

PubMed1993

Conversion of alpha-helices into beta-sheets features in the formation of the scrapie prion proteins.

Prions are composed largely, if not entirely, of prion protein (PrPSc in the case of scrapie). Although the formation of PrPSc from the cellular prion protein (PrPC) is a post-translational process, no candidate chemical modification was identified, suggesting that a conformational change features in PrPSc synthesis. To assess this possibility, we purified both PrPC and PrPSc by using nondenaturing procedures and determined the secondary structure of each. Fourier-transform infrared (FTIR) spectroscopy demonstrated that PrPC has a high alpha-helix content (42%) and no beta-sheet (3%), findings that were confirmed by circular dichroism measurements. In contrast, the beta-sheet content of PrPSc was 43% and the alpha-helix 30% as measured by FTIR. As determined in earlier studies, N-terminally truncated PrPSc derived by limited proteolysis, designated PrP 27-30, has an even higher beta-sheet content (54%) and a lower alpha-helix content (21%). Neither PrPC nor PrPSc formed aggregates detectable by electron microscopy, while PrP 27-30 polymerized into rod-shaped amyloids. While the foregoing findings argue that the conversion of alpha-helices into beta-sheets underlies the formation of PrPSc, we cannot eliminate the possibility that an undetected chemical modification of a small fraction of PrPSc initiates this process. Since PrPSc seems to be the only component of the "infectious" prion particle, it is likely that this conformational transition is a fundamental event in the propagation of prions.

Animals↗

PubMed1993

Ablation of the prion protein (PrP) gene in mice prevents scrapie and facilitates production of anti-PrP antibodies.

Mice, homozygous for prion protein (PrP) gene ablation (Prn-p0/0), develop normally and remain well > 500 days after inoculation with murine scrapie prions. In contrast, wild-type mice developed scrapie < 165 days after inoculation and most Prn-p0/+ mice, heterozygous for disruption of the PrP gene, exhibited signs of central nervous system dysfunction between 400 and 465 days after inoculation. In situ immunoblots showed widespread deposition of scrapie PrP (PrPSc) in the brains of both wild-type Prn-p+/+ and Prn-p0/+ mice, while neither cellular PrP (PrPC) nor PrPSc was detected in the brains of Prn-p0/0 mice. In contrast to Prn-p+/+ and Prn-p0/+ mice, Prn-p0/0 mice failed to propagate prion infectivity as measured by bioassays. Syrian hamster (SHa) PrP transgenes rendered Prn-p0/0 mice susceptible to prions containing SHaPrPSc. Immunization of Prn-p0/0 mice with purified, infectious mouse or SHa prions dispersed in Freund's adjuvant produced antisera that bound mouse, SHa, and human PrP on Western blots. Presumably, the lack of PrPC expression in Prn-p0/0 mice prevents them from becoming tolerant to the immunogen. The resistance of Prn-p0/0 mice to developing scrapie after inoculation with murine prions supports the hypothesis that PrPSc is essential for both transmission and pathogenesis of the prion diseases.

Animals↗

PubMed1993

Attempts to restore scrapie prion infectivity after exposure to protein denaturants.

A wealth of experimental evidence argues that infectious prions are composed largely, if not entirely, of the scrapie isoform of the prion protein. We attempted to restore scrapie infectivity after exposure to protein denaturants including urea, chaotropic salts, and SDS. None of the procedures restored infectivity. Dialysis to remove slowly chaotropic ions and urea failed to restore scrapie infectivity. Attempts to create monomers of the scrapie isoform of the prion protein under nondenaturing conditions using a wide variety of detergents have been unsuccessful, to date, except for one report claiming that scrapie infectivity could be recovered from 12% polyacrylamide gels after SDS/PAGE [Brown, P., Liberski, P. P., Wolff, A. & Gajdusek, D. C. (1990) Proc. Natl. Acad. Sci. USA 87, 7240-7244]. We found that < 0.001% of the infectious prion titer could be recovered from the region of a polyacrylamide gel where the denatured proteinase K-resistant core of the scrapie isoform of the prion protein and other 30-kDa proteins migrate. We conclude that under the denaturing conditions used for SDS/PAGE, the scrapie isoform of the prion protein is denatured and little or no renaturation occurs upon injection of fractions eluted from gels into animals for bioassays.

Animals↗

PubMed1993

[Primary hyperparathyroidism in 2 adolescents].

The authors report on two cases of primary hyperparathyroidism (PHP) in adolescents. In a 15-year-old boy, the clinical picture included skeletal, dental, renal and psychological manifestations. In the second case, the first symptom was urolithiasis at age 12; following a period without any important clinical event, the diagnosis was established when the patient was 18. In both cases, increased calcium and low phosphorus plasma levels associated to moderately elevated plasma parathyroid hormone levels were noted. CT scan and ultrasounds were normal but MRI showed an enlarged gland in the second case. The surgical exploration of the neck revealed an adenoma in the first case and a hyperplastic gland in the second one. Surgery was followed by an immediate improvement of both clinical and laboratory findings. These observations bring us to examine the spectrum of PHP in childhood, the difficulties in biological diagnosis and localizing techniques, and the recent results of surgical treatment.

Adolescent↗

PubMed1991

Scrapie prion rod formation in vitro requires both detergent extraction and limited proteolysis.

Scrapie prion infectivity can be enriched from hamster brain homogenates by using limited proteolysis and detergent extraction. Purified fractions contain both scrapie infectivity and the protein PrP 27-30, which is aggregated in the form of prion rods. During purification, PrP 27-30 is produced from a larger membrane protein, PrPSc, by limited proteolysis with proteinase K. Brain homogenates from scrapie-infected hamsters do not contain prion rods prior to exposure to detergents and proteases. To determine whether both detergent extraction and limited proteolysis are required for the formation of prion rods, microsomal membranes were prepared from infected brains in the presence of protease inhibitors. The isolated membranes were then detergent extracted as well as protease digested to evaluate the effects of these treatments on the formation of prion rods. Neither detergent (2% Sarkosyl) extraction nor limited proteinase K digestion of scrapie microsomes produced recognizable prion amyloid rods. Only after combining detergent extraction with limited proteolysis were numerous prion rods observed. Rod formation was influenced by the protease concentration, the specificity of the protease, and the duration of digestion. Rod formation also depended upon the detergent; some combinations of protease and detergent did not produce prion amyloid rods. Similar results were obtained with purified PrPSc fractions prepared by repeated detergent extractions in the presence of protease inhibitors. These fractions contained amorphous structures but not rods; however, prion rods were produced upon conversion of PrPSc to PrP 27-30 by limited proteolysis. We conclude that the formation of prion amyloid rods in vitro requires both detergent extraction and limited proteolysis. In vivo, amyloid filaments found in the brains of animals with scrapie resemble prion rods in their width and their labeling with prion protein (PrP) antisera; however, filaments are typically longer than rods. Whether limited proteolysis and some process equivalent to detergent extraction are required for amyloid filament formation in vivo remains to be established.

Animals↗

PubMed1977

Hemorrhagic fever with renal syndrome: report of 11 observations.

Based on the observation of 11 patients (10 males and 1 female), the occurrence of hemorrhagic fever with renal syndrome in two new geographic areas of Romania is reported. Two patients died within several hours after admission. The other nine recovered gradually. In four patients hemodialysis was necessary. A complete recovery of renal functions one year after onset could be proved in four patients. The clinical, laboratory, morphopathological (necroptic and bioptic), epidemiologic and evolutive characteristics of the disease, especially the main features supporting the diagnosis of hemorrhagic fever with renal syndrome, are discussed.

Adult↗

PubMed1973