Israel Medical Association Journal

Objectives: To describe the types of endothelial cell organelles involved in vascular permeability in drug-induced acute urticaria (DIAU).

Methods: Seven patients with DIAU were enrolled in the study. Biopsies of urticarial lesions and apparently normal skin were performed. The 14 collected fragments were processed with immunogold electron microscopy using single stains for tryptase and factor XIIIa (FXIIIa) and double immunogold labeling for both tryptase and FXIIIa.

Results: Some sections demonstrated mast cells in the degranulation process, in both anaphylactic and piecemeal degranulation. After double immunogold staining, 10 nm (FXIIIa) and 15 nm (tryptase) gold particles were both present, covering the granules in the mast cells, indicating that both tryptase and FXIIIa were localized within the granules of these cells. Interestingly, we found strong evidence of the presence of caveolae and vesico-vacuolar organelles (VVOs) in the endothelial cells of the biopsies. In addition to these findings, we were able to demonstrate the presence of tryptase and FXIIIa in the endothelial cells, in urticarial lesions and in apparently normal skin.

Conclusions: VVOs are present in the endothelial cells of post-capillary venules in DIAU. This is the first report on the expression of FXIIIa and tryptase in the cytoplasm of endothelial cells in urticaria. 

Objectives: To determine the effect of the Dead Sea climatotherapy on the quality of life of patients with psoriasis vulgaris and psoriatic arthritis.

Methods: A total of 119 patients participated in an observational prospective study carried out at the Deutsches Medizinisches Zentrum clinic, a medical skin care center specializing in climatotherapy. The patients completed questionnaires (Skindex-29) to quantify their quality of life at different time points: the day of arrival, the day of departure, and 3 and 6 months after the end of treatment.

Results: Marked improvement in the quality of life scores was measured between the time of arrival to time of departure and to 3 months after the end of treatment.

Conclusions: Dead Sea climatotherapy has a significant positive influence on the quality of life of patients with psoriasis vulgaris and psoriatic arthritis.

Scientific journals are ethically bound to cite Professor Dr. Carl Clauberg's Nazi medical crimes against humanity whenever the eponym Clauberg is used. Modern articles still publish the eponym citing only the rabbit bioassay used in developing progesterone agonists or antagonists for birth control. Clauberg’s Nazi career is traced to his having subjected thousands of Jewish women at the Ravensbruck and Auschwitz-Birkenau death camps to cruel, murderous sterilization experiments that are enthusiastically described by incriminating letters (reproduced here) between him and the notorious Nazi Reichsführer-SS Heinrich Himmler. The experiments were carried out in women’s Block 10 in Auschwitz-Birkenau where Clauberg’s colleague Dr. Josef Mengele worked alongside. After Germany lost World War II in 1945 Mengele fled to South America, where he lived to an old age. Clauberg was caught by Russian soldiers, put on trial in the Soviet Union for his crimes against humanity, and imprisoned in 1948. In 1955 he was repatriated to Germany, once again imprisoned for his crimes, and belatedly expelled from the German Medical Association. To estimate the contemporary usage of the names Mengele and Clauberg, Internet hits were recorded for Clauberg C or Mengele J (with and without adding the term Auschwitz) with the Google and Scirus search engines. The ratios of hits for combinations of these terms reveal that relative to Mengele, Clauberg’s name is barely known. We propose that journals and books printing the eponym Clauberg cite its derivation and reference to the convicted Nazi criminal. The present article can serve for such citations.

Background: Transthyretin (TTR)-associated familial amyloid polyneuropathy (FAP) is an autosomal dominant multisystem disease with neurological and extra-neurological manifestations. It is caused by various mutations in the TTR gene leading to the formation of insoluble amyloid.

Objectives: To describe the clinical and genetic findings in patients with TTR-associated FAP in Israel.

Methods: We evaluated eight patients clinically and genetically during the years 2006 to 2011.

Results: At onset, all the patients exhibited sensory loss of the lower and upper limbs, five patients experienced muscle pain, and one patient had lower limb weakness. Five patients had autonomic nervous system manifestations, and four demonstrated evidence of amyloid cardiomyopathy. Nerve conduction studies showed sensorimotor axonal neuropathy in all patients. Sural nerve biopsies were obtained in five patients; only three biopsies revealed amyloid deposit. In four patients of Yemenite descent, genetic analysis of the TTR gene demonstrated ser77tyr mutation. One patient of Tunisian descent and one Ashkenazi patient harbored the val30met mutation. One patient of Iranian descent showed val32ala mutation, and another Ashkenazi patient showed phe33leu mutation.

Conclusions: TTR-associated FAP is a progressive and fatal disease that exists in the Israeli population and is unproportionally common among Yemenite Jews. This disease may be under-diagnosed and should be considered in the differential diagnosis of any patient with rapidly progressive neuropathy, especially with autonomic involvement or extra-neural features. The absence of amyloid in nerve biopsy should not rule out the diagnosis.  
 

The role of carbon in the development of life and as the structural backbone of all organisms is universally accepted and an essential part of evolution. However, the molecular basis is largely unknown and the interactions of carbon with nitrogen and oxygen in space are enigmatic. In 1985, the previously unknown form of carbon, coined fullerene, was discovered. We hypothesize that by virtue of the unique properties of fullerene, this hollow, ultra-robust, large, purely carbon molecule was the earliest progenitor of life. It acted as a stable universal biologic template on which small molecules spontaneously assembled and then formed, by further assembly, a surface mantle (here termed rosasome) of larger molecules. We submit that this process, by its inherent flexibility, initiated evolution, allowing the emergence of parallel diverse rosasome lines responding selectively to varying spatial environments. For example, rosasomal lines mantled with nucleotide and peptide layers are conceived as primordial forerunners of the ubiquitous ribosome. Moreover, the parallel independent and interdependent evolution of rosasome lines would be more rapid than sequential development, refute precedence of either DNA or RNA, and explain the evolution of integration of two subunits with different structures and functions in ribosomes and of the triplet nature of the codon. Based on recent astronomical data, this hypothesis supports the concept that life is not a singularity. This concept also suggests a potential vehicle for therapeutics, biotechnology and genetic engineering.

Background: During an influenza pandemic, clinicians need easily available clinical and laboratory criteria to distinguish influenza from similar respiratory illnesses. We compared A/H1N1/2009-polymerase chain reaction (PCR)-positive and matched PCR-negative hospitalized patients with suspected H1N1 influenza to identify factors that could assist physicians at patient admission.

Objectives: To identify factors significantly associated with A/H1N1/2009 infection.

Methods: A group of 145 patients with PCR-confirmed A/H1N1 2009 influenza admitted between 27 May 2009 and 3 December 2009 was matched with 145 PCR-negative patients by age, epidemiological week and pregnancy status. Epidemiological and clinical parameters and radiological findings on initial chest X-ray were compared between the two groups.

Results: Asthma (PCR+ 26%, PCR- 12%, P = 0.006) and military service (PCR+ 13%, PCR- 4%, P = 0.15) were associated with PCR-positive status in non-pregnant patients. At presentation, fever, cough, myalgia and fulfilling the pandemic influenza case definition were significantly more frequent in non-pregnant PCR+ patients (62/90/43/59% in PCR+ versus 38/69/30/35% in PCR-). In pregnant patients, fever and fulfilling the case definition were significantly associated with PCR-positive status. Mean leukocyte and absolute lymphocyte counts were significantly lower in both pregnant and non-pregnant PCR-positive patients. Significantly more PCR-negative non-pregnant patients (43% vs. 22% PCR+, P = 0.004) had abnormal chest X-ray (CXR) findings on presentation. In PCR-positive patients, patchy consolidation and interstitial infiltrates were the most common abnormalities.

Conclusions: Under the conditions generated by the A/H1N1/2009 pandemic, radiological findings did not distinguish reliably between influenza and other febrile respiratory illnesses. Asthma, military service, the pandemic case definition (particularly fever, cough and myalgia) and lymphopenia were associated with confirmed H1N1 infection.
 

Background: Atherosclerosis is a well-established inflammatory disease in which T helper 1 (Th1) cells play a key role. Regulatory T (Treg) cells drive a shift from Th1 to Th2 response and were shown to be reduced in atherosclerosis. ST2/interleukin (IL)-33 signal was found to promote Th2 response, attenuating atherosclerotic plaque progression.

Objectives: To evaluated the effect of IL-33 on Treg cell number.

Methods: We employed flow cytometry to determine Treg cell number, as well as ST2 levels, among splenocytes of C57BL/6J vs ApoE-/- mice. Soluble ST2 (sST2) levels were detected by enzyme-linked immunosorbent assay. 

Results: IL-33 contributed to an increase in Treg cells, but this association was attenuated in ApoE knockout (ApoE-/-) atherosclerotic mice. As a possible mechanism we demonstrated a reduction in the levels of CD4+ST2+ cells by flow cytometry, which is cotemporary to the previously described decrease in Treg cells in ApoE-/- mice. Additionally, the serum level of the soluble ST2 (sST2) decoy receptor was higher in ApoE-/- mice than in control animals.

Conclusions: Our results suggest that a repressed ST2/IL-33 signaling may contribute to the decrease in Treg cells observed in atherosclerosis.