• IMA sites
  • IMAJ services
  • IMA journals
  • Follow us
  • Alternate Text Alternate Text
עמוד בית
Mon, 21.09.26

Search results


September 2002
Aliza Amiel, PhD, Orit Reish, MD, Elena Gaber, PhD, Ronit Masterman, MD, Tally Tohami, MSc and Moshe D. Fejgin, MD

Background: While most allelic pairs of DNA replicate synchronously during the S phase of the cell cycle, some genes normally replicate asynchronously, i.e., genes on the X chromosome and imprinted genes. The replication control mechanism is unknown but was shown to be impaired in malignancies and chromosomal trisomies where replication pattern becomes asynchronous.

Objectives: To determine the level of asynchronization in replication timing of cells from patients with microdeleted genomes.

Methods: We applied monocolor fluorescent in situ hybridization with different probes on leukocytes from microdeleted genomes.

Results: All samples derived from the microdeleted genomes showed significantly higher levels of an asynchronized pattern compared to normal individuals.

Conclusions: Even a “small” genetic imbalance (microdeletion) can interfere with gene replication and cell cycle progression, as previously shown in full trisomies.
 

Kelen C.R. Malmegrim, BSc2, Ger J.M. Pruijn, PhD and Walther J. van Venrooij, PhD

Recent studies have implicated the dying cell as a potential reservoir of modified autoantigens that may initiate and drive systemic autoimmunity in susceptible hosts. The uridine-rich small nuclear ribonucleoprotein complex is a common target for autoantibodies present in the serum of patients with systemic lupus erythematosus and SLE[1]-overlap syndromes. Four modifications occurring in this complex during apoptosis have been described to date: the caspase-mediated cleavage of the U1-70K protein, the U1 RNA and the Sm-F protein, and the association with hyperphosphorylated SR proteins. In addition, the U1 snRNP[2] complex has been shown to translocate from its normal subcellular localization to apoptotic bodies near the surface of cells undergoing apoptosis. This redistribution might facilitate exposure of the modified components of the U1 snRNP complex to the immune system when the clearance of apoptotic cell remnants is somehow disturbed. The modifications in the U1 snRNP components during apoptosis might represent the initial epitopes to which an immune response is generated and may be the trigger for the production of autoantibodies to this complex in patients with SLE or SLE-overlap syndromes. Therefore, it can be hypothesized that the exposure of elevated levels of apoptotically modified U1 snRNP to the immune system of a genetically susceptible individual might lead to the breaking of immunologic tolerance towards the U1 snRNP complex.

____________________________________


[1] SLE = systemic lupus erythematosus

[2] U snRNP = uridine-rich small nuclear ribonucleoprotein

Zvi Fireman, MD, Arkady Glukhovsky, PhD, Harold Jacob, MD, FACG, Alexandra Lavy, MD, Shlomo Lewkowicz, DSc and Eitan Scapa, MD
Mogher Khamaisi, PhD and Itamar Raz, MD
Gisele Zandman-Goddard, MD and Miri Blank, PhD
August 2002
Alla Reitman, MD, Ilana Friedrich, MD, Ami Ben-Amotz, PhD and Yishai Levy, MD

Background: Obesity is among the well-established risk factors for cardiovascular morbidity and mortality. However, the exact mechanisms are not well understood. Low concentrations of vitamins (fat soluble antioxidants and B vitamins) are linked to accelerated atherosclerosis through increased oxidative stress and homocysteine.

Objective: To compare plasma antioxidant vitamins (carotenoids and vitamin E), B vitamins (folic acid and B12) and homocysteine – all linked to increased cardiovascular morbidity – between patients with severe obesity and lean control subjects.

Methods: We investigated plasma carotenoids, vitamin E, folic acid, B12, and homocysteine in 25 obese patients and their age-matched controls (body mass index 38 ± 3 vs. 21 ± 2 kg/m2), respectively), related to BMI[1] and plasma insulin.

Results: Patients with obesity had normal B vitamins and a non-significant decrease in plasma homocysteine as compared to controls (9.4 ± 2.6 vs. 11.4 ± 4.8 mmol/L, P = 0.07). There was a significant decrease in both plasma carotenoids and vitamin E (0.69 ± 0.32 vs. 1.25 ± 0.72 and 24 ± 10 vs. 33 ± 14 mg/ml, respectively; P < 0.01). Both vitamins were inversely related to BMI and plasma insulin, which was significantly increased in patients with obesity (22 ± 21 vs. 6 ± 2 mU/ml, P < 0.01).

Conclusions: Obese patients with BMI above 35 kg/m2 show low plasma antioxidants (carotenoids and vitamin E). This may result in increased oxidative stress and consequently enhanced atherosclerosis in these patients.






[1] BMI = body mass index


Raanan Shamir, MD, Rami Eliakim, MD, Nitza Lahat, PhD, Esther Sobel, MSc and Aaron Lerner, MD, MHA

Background: Celiac disease is common in both children and adults. Small intestinal biopsy is mandatory for establishing a diagnosis. Anti-endomysial antibodies, detected by immunofluorescence, have a sensitivity and specificity close to 100% in the diagnosis of CD[1]. Recently, tissue transglutaminase has been identified as the target autoantigen of antibodies against endomysium, and TTG[2] antibodies are comparable to EMA-IMF[3] in the diagnosis of CD.

Objective: To evaluate a new enzyme-linked immunosorbent assay kit for EMA, compared to EMA-IMF and TTG antibodies in the diagnosis of CD.

Methods: Our study population included all subjects with positive EMA-IMF who underwent intestinal biopsy (n=21). From the same sera, TTG antibodies and EMA-ELISA[4] were determined, and all antibody results were compared to the biopsy findings.

Results: EMA-IMF was able to predict biopsy findings of CD in 19 of 21 cases (90.5%). When patients with biopsy findings compatible with CD and positive EMA-IMF (n=19) were tested for EMA-ELISA and TTG antibodies, 18 of the 19 were positive for both EMA-ELISA and TTG antibodies. A significant correlation was found between EMA-ELISA and TTG antibody titers (r = 0.74, P < 0.001).

Conclusions: Our study demonstrates that EMA-ELISA is comparable to TTG antibodies in the diagnosis of CD, and supports the use of EMA-ELISA as a serologic marker for this disease.


_______________________

[1]
CD = celiac disease

[2] TTG = tissue transglutaminase

[3] EMA-IMF = anti-endomysial antibodies measured by immunofluorescence

[4] ELISA = enzyme-linked immunosorbent assay

Rachel Goldwag, MSW, Ayelet Berg, PhD, Dan Yuval, PhD and Jochanan Benbassat, MD

Background: Patient feedback is increasingly being used to assess the quality of healthcare.

Objective: To identify modifiable independent determinants of patient dissatisfaction with hospital emergency care.

Methods: The study group comprised a random sample of 3,152 of the 65,966 adult Israeli citizens discharged during November 1999 from emergency departments in 17 of the 32 acute care hospitals in Israel. A total of 2,543 (81%) responded to a telephone survey tht used a structured questionnaire. The ndependent variables included: hospital characteristics, patient demographic variables, patient perception of care, self-rated health status, problem severity, and outcome of care. The dependent variable was dissatisfaction with overall ED[1] experience on a 1–5 Likert-type scale dichotomized into not satisfied (4 and 5) and satisfied (1,2 and 3).

Results: Eleven percent of the population reported being dissatisfied with their emergency room visit. Univariate analyses revealed that dissatisfaction was significantly related to ethnic group, patient education, hospital identity and geographic location, perceived comfort of ED facilities, registration expediency, waiting times, perceived competence and attitudes of caregivers, explanations provided, self-rated health status, and resolution of the problem that led to referral to the ED. Multivariate analyses using logistic regressions indicated that the four most powerful predictors of dissatisfaction were patient perception of doctor competence and attitudes, outcomes of care, ethnicity, and self-rated health status.

Conclusions: Attempts to reduce dissatisfaction with emergency care should focus on caregiver conduct and attitudes. It may also be useful to improve caregiver communication skills, specifically with ethnic minorities and with patients who rate their health status as poor.


_____________________________

[1]
ED = emergency department

Fabio Broglio, MD, Emanuela Arvat, MD, Andrea Benso, MD, Cristina Gottero, MD, Flavia Prodam, MD, Riccarda Granata, PhD, Mauro Papotti, MD, Giampiero Muccioli, PhD, Romano Deghenghi, PhD and Ezio Ghigo, MD

Ghrelin, a 28 amino acid acylated peptide predominantly produced by the stomach, displays strong growth hormone-releasing activity mediated by the hypothalamus-pituitary GH[1] secretagogue receptors that were found to be specific for a family of synthetic, orally active GH secretagogues. The discovery of ghrelin brings us to a new understanding of the regulation of GH secretion. However, ghrelin is much more than simply a natural GH secretagogue. It also acts on other central and peripheral receptors and exhibits other actions, including stimulation of lactotroph and corticotroph secretion, orexigenia, influences gastroenteropancreatic functions, and has metabolic, cardiovascular and anti-proliferative effects. Knowledge of the whole spectrum of biologic activities of this new hormone will provide new understanding of some critical aspects of neuroscience, metabolism and internal medicine. In fact, GHS[2] were born more than 20 years ago as synthetic molecules, eliciting the hope that orally active GHS could be used to treat GH deficiency as an alternative to recombinant human GH. However, the dream did not become reality and the usefulness of GHS as an anabolic anti-aging intervention restoring the GH/IGF-I[3] axis in somatopause is still unclear. Instead, we now face the theoretic possibility that GHS analogues acting as agonists or antagonists could become candidate drugs for the treatment of pathophysiologic conditions in internal medicine totally unrelated to disorders of GH secretion. 




---------------------------------------

[1]
GH = growth hormone

[2] GHS = GH secretagogues

[3] GH/IGF-1 = growth hormone/insulin-like growth factor-I

Gerard Espinosa, MD, Ricard Cervera, MD, PhD, Joan-Carles Reverter, MD, PhD, Dolors Tassies, MD, PhD, Josep Font, MD, PhD and Miguel Ingelmo, MD, PhD
Wendy Chen, MSW, Ruth Balaban, MA, RN, Varda Stanger, PhD, Ra’aya Haruvi, MSW, Shmuel Zur, MD and Arie Augarten, MD
Shai Izraeli, MD and Gideon Rechavi, MD, PhD
Bella Bielorai, MD, Hana Golan, MD, Gideon Rechavi, MD, PhD and Amos Toren, MD
Legal Disclaimer: The information contained in this website is provided for informational purposes only, and should not be construed as legal or medical advice on any matter.
The IMA is not responsible for and expressly disclaims liability for damages of any kind arising from the use of or reliance on information contained within the site.
© All rights to information on this site are reserved and are the property of the Israeli Medical Association. Privacy policy

2 Twin Towers, 35 Jabotinsky, POB 4292, Ramat Gan 5251108 Israel