Resident cells of the myocardium: more than spectators in cardiac injury, repair and regeneration.

Multiple resident cell types contribute to maintaining the structure and physiological function of the heart over the life course. Cardiomyocyte proliferation supports scar free regeneration in the neonatal heart following injury, but a lower rate of proliferation in the adult necessitates replacement by a collagen scar to maintain ventricular integrity. In this short review we discuss recent studies that have identified novel roles for non-myocyte resident cells and the extracellular matrix in supporting repair, as well as cardiomyocyte and vascular regeneration, following myocardial infarction.

Pericytes, integral components of adult hematopoietic stem cell niches.

The interest in perivascular cells as a niche for adult hematopoietic stem cells (HSCs) is significantly growing. In the adult bone marrow (BM), perivascular cells and HSCs cohabit. Among perivascular cells, pericytes are precursors of mesenchymal stem/stromal cells (MSCs) that are capable of differentiating into osteoblasts, adipocytes and chondrocytes. In situ, pericytes are recognised by their localisation to the abluminal side of the blood vessel wall and closely associated with endothelial cells, in combination with the expression of markers such as CD146, neural glial 2 (NG2), platelet derived growth factor receptor ß (PDGFRß), α-smooth muscle actin (α-SMA), nestin (Nes) and/or leptin receptor (LepR). However, not all pericytes share a common phenotype: different immunophenotypes can be associated with distinct mesenchymal features, including hematopoietic support. In adult BM, arteriolar and sinusoidal pericytes control HSC behaviour, maintenance, quiescence and trafficking through paracrine effects. Different groups identified and characterized hematopoietic supportive pericyte subpopulations using various markers and mouse models. In this review, we summarize recent work performed by others to understand the role of the perivascular niche in the biology of HSCs in adults, as well as their importance in the development of therapies.

Photodynamic therapy using topical 5-aminolaevulinic acid vs. surgery for basal cell carcinoma.

BACKGROUND: Photodynamic therapy (PDT) is an attractive modality for the treatment of BCC, based on its generally favorable efficacy, adverse effect profile and its excellent cosmetic outcome. OBJECTIVES: The purpose of the study is to compare the efficacy and cosmetic outcome of photodynamic therapy with topical 5-aminolaevulinic acid (ALA-PDT) vs. simple excision surgery for superficial and nodular basal cell carcinoma (BCC). METHODS: A total of 72 patients, 32 with 48 lesions, were treated with ALA- PDT, and 40 with 46 lesions treated by excision were included in this prospective, comparative, controlled, clinical study. The patients have been followed for 16-37 months (mean 25 months). The PDT was performed in combination with 5-aminolaevulinic acid twice, one month apart. Surgical excision was performed under local anesthesia with a 3-mm margin, followed by histological examination. The cosmetic outcome was evaluated by the physician according to a 4-point scale. RESULTS: Overall 94 BCC were treated. Complete healing rates did not differ significantly between groups, P = 0.64 (46/48 [95.83%] lesions treated with PDT vs. 44/46 [95.65%] lesions with surgery). In the first 12 months of follow-up, 4 lesions had recurred, 2 of which were in the PDT group while 2 lesions after surgery. The mean follow-up was 25 months. The recurrence rate in the ALA-PDT group was 4.16% vs. 4.34% in the surgery group, p = 0.64. The cosmetic outcome was superior for ALA-PDT at all time points. At 12 months, 100% lesions treated with ALA-PDT had an excellent or good cosmetic outcome, according to the investigator, compared with 88.86% with surgery, P = 0.01. CONCLUSION: ALA-PDT offers a similarly high efficacy, and a better cosmetic outcome than simple excision surgery in the treatment of BCC.

The biochemistry of hematopoietic stem cell development.

BACKGROUND: The cornerstone of the adult hematopoietic system and clinical treatments for blood-related disease is the cohort of hematopoietic stem cells (HSC) that is harbored in the adult bone marrow microenvironment. Interestingly, this cohort of HSCs is generated only during a short window of developmental time. In mammalian embryos, hematopoietic progenitor and HSC generation occurs within several extra- and intraembryonic microenvironments, most notably from 'hemogenic' endothelial cells lining the major vasculature. HSCs are made through a remarkable transdifferentiation of endothelial cells to a hematopoietic fate that is long-lived and self-renewable. Recent studies are beginning to provide an understanding of the biochemical signaling pathways and transcription factors/complexes that promote their generation. SCOPE OF REVIEW: The focus of this review is on the biochemistry behind the generation of these potent long-lived self-renewing stem cells of the blood system. Both the intrinsic (master transcription factors) and extrinsic regulators (morphogens and growth factors) that affect the generation, maintenance and expansion of HSCs in the embryo will be discussed. MAJOR CONCLUSIONS: The generation of HSCs is a stepwise process involving many developmental signaling pathways, morphogens and cytokines. Pivotal hematopoietic transcription factors are required for their generation. Interestingly, whereas these factors are necessary for HSC generation, their expression in adult bone marrow HSCs is oftentimes not required. Thus, the biochemistry and molecular regulation of HSC development in the embryo are overlapping, but differ significantly from the regulation of HSCs in the adult. GENERAL SIGNIFICANCE: HSC numbers for clinical use are limiting, and despite much research into the molecular basis of HSC regulation in the adult bone marrow, no panel of growth factors, interleukins and/or morphogens has been found to sufficiently increase the number of these important stem cells. An understanding of the biochemistry of HSC generation in the developing embryo provides important new knowledge on how these complex stem cells are made, sustained and expanded in the embryo to give rise to the complete adult hematopoietic system, thus stimulating novel strategies for producing increased numbers of clinically useful HSCs. This article is part of a Special Issue entitled Biochemistry of Stem Cells.

Brown adipocyte progenitor population is modified in obese and diabetic skeletal muscle.

Brown adipose tissue mitochondria express the unique thermogenic uncoupling protein-1. Recently, brown adipocyte progenitors have been identified in the CD34+ cell population of human skeletal muscle. The aims of this study were firstly to determine if obesity and diabetes have altered amounts of muscle brown adipocyte progenitors and, secondly, to establish if the latter are correlated with clinical parameters of obesity and diabetes. Body mass index (BMI), plasma glucose, insulin, cholesterol and triglycerides as well as homeostasis model assessment were measured in lean (n=10), obese (n=18) and obese-diabetic (n=15) subjects and muscle biopsies were taken from the rectus abdominus. CD34 being also expressed on endothelial cells, we measured CD31, another endothelial marker, and expressed the brown adipocyte progenitors, as the CD34/CD31 mRNA ratio. The latter was significantly reduced in the obese vs lean subjects suggesting a smaller pool of brown adipocyte progenitors. More strikingly, for lean and obese subjects negative correlations were observed between the CD34/CD31 mRNA ratios and BMI, fasting insulin levels and homeostasis model assessment. These correlations highlight the potential physiological relevance of the muscle CD34/CD31 mRNA ratio.

Transport and current noise characteristics of a T-shape double-quantum-dot system.

We consider the transport and the noise characteristics for the case of a T-shape double-quantum-dot system using the equation of motion method. Our theoretical results, obtained in an approximation equivalent to the Hartree-Fock approximation, account for non-zero on-site Coulomb interaction in both the detector and side dots. The existence of a non-zero Coulomb interaction implies an additional two resonances in the detector's dot density of states and thereafter affects the electronic transport properties of the system. The system's conductance presents two Fano dips as a function of the energy of the localized electronic level in the side dot. The Fano dips in the system's conductance can be observed for both strong (fast detector) and weak coupling (slow detector) between the detector dot and the external electrodes. Due to stronger electronic correlations, the noise characteristics in the case of a slow detector are much higher. This setup may be of interest for the practical realization of qubit states in quantum dot systems.

Spontaneous external fistula of a hydatid liver cyst in a diabetic patient.

BACKGROUND: The liver is the most common site of hydatid disease. Complications like cyst rupture and infection may occur, sites of rupture including: bile ducts, gastrointestinal tract, bronchi, peritoneal and pleural cavity. Rupture into the subcutaneous tissue followed by external fistula is an extremely rare complication. CASE REPORT: A 71-year-old diabetic woman was referred for a progressive growing mass in the right hypochondrium, with a central fistula draining clear liquid with cystic elements and white membranes. No history of fever or jaundice was present. Abdominal ultrasound (followed by CT scan) revealed a liver hydatid cyst in the right lobe, in contact with the anterior abdominal wall, and a parietal fistula track. Cystic fluid exam showed protoscolices and serological ELISA test was positive for hydatid disease. At surgery, the lesion was approached through an incision starting from the fistula site. Partial cystectomy and external drainage of the residual cavity were performed. The fistula track was totally resected. After an uneventful recovery and six months of anti - parasitic treatment, the patient is symptoms- free (3 years after surgery). CONCLUSIONS: Spontaneous cyst-cutaneous fistula is an extremely rare complication of hydatid liver cyst, usually occurring silently, in elder people. Surgery is required to achieve complete evacuation of the cyst contents and resolution of the residual cavity. To the best of our knowledge, this is the seventh case published, and the first one in the Romanian literature.

[Staphylococcal anatoxin, an alternative in the treatment of endogenous uveitis]. / Anatoxina stafilococica, o alternativa în tratamentul uveitei endogene.

The paper presents one clinical study effected by fourty-four patients with endogenous uveitis which beneficiary of a general treatment with staphylococcal anatoxin. The conclusions of the study impose that one effective treatment is obtained at the young patients with anterior, acute uveitis with moderate inflammatory phenomenon and what present one effective answer of the lymphocyte T by interleukin 1. The application of the treatment suppose several exams reminiscent of the immunologic status especially of the cellular immunology.

In vivo effects of thymic hormones (Imunotim) on immunologic parameters of patients with secondary immunodeficiency diseases.

In previous papers we revealed the immuno-restorative capacity of thymic hormones both in vitro and in vivo. This paper is concerned with the investigation in a phase I trial of the effects of a thymic extract (Imunotim) prepared in the Cantacuzino Institute, Bucharest upon patients with immunodeficiencies manifest as recurrent or persistent infections resistant to classical treatments. Twenty five testings were performed on 23 patients with secondary immunodepressions: carcinomas with immunodepressions following the acute phase of the disease or cytoreductive treatments (10 cases), allergic and autoimmune conditions (3 cases) and frequent, recurrent infections with prolonged evolution. In 73.9% of cases (17/23) after administration of Imunotim per os the immunologic parameters showed a tendency to return to normal values. In patients with low pre-therapy values the following were noticed: a remarkable increase of the number of lymphocytes from 1317.2 +/- 506.40 to 1961.1 +/- 899.11 (p < 0.01), of PMN from 1401.7 +/- 444.21 to 2651.0 +/- 755.31 (p < 0.01), of the absolute number of B lymphocytes from 192.0 +/- 79.00 to 444.8 +/- 299.75 (p < 0.05); the rise in the rate and absolute number of total T lymphocytes (628.2 +/- 192.81, 1041.0 +/- 441.84, respectively; p < 0.05), T helper (from 29.84 +/- 12.75% to 44.14 +/- 18.76%, respectively from 421.6 +/- 127.29 to 1058.7 +/- 411.05; p < 0.01 respectively p < 0.02) and the rise of the absolute number of T suppressor/cytotoxic lymphocytes from 92.8 +/- 97.11 to 368.3 +/- 368.53 (p < 0.05). In some patients with lymphocytosis and adenopathies the absolute lymphocyte number and the maturation of the lymphocyte populations and subpopulations in blood showed a decline. Individual variations could be noticed even within one and the some primary affection.

Translocations (4p+; 6q-) and (12q-; Xp+) in blastic phase of a Ph1-positive chronic myeloid leukemia.

This paper reports a 28-year-old woman with Philadelphia chromosome (Ph1)-positive chronic myeloid leukemia (CML) who developed two marrow cell lines during the blastic phase: one with the translocation (12;X) (q 11;p22) and the other with the translocation (4;6) (p 16;q 25). The literature on involvement of chromosomes 12 and X in translocations and the appearance of 6 q- aberration in CML is summarized. The relationship between the 6 q-aberration and the blast cells with lymphoid appearance in the plastic phase of CML is discussed.

Spontaneous release of leukocyte migration inhibition factor (LMIF) by lymphocytes in chronic lymphatic leukemia patients.

Leukocyte migration inhibition factor (LMIF) activity expressed as a migration index was studied in sera of 13 chronic lymphatic leukemia (CLL) patients and 14 healthy subjects. LMIF activity was present in 92.8% of CLL patients and 14% of controls. The LMIF activity of lymphocyte culture supernatants in the same patients and 7 controls was also studied. A LMIF-like activity was found both, in the sera and phytohemagglutinin (PHA) unstimulated cell supernatants in 9 of 13 patients (69.2%). These results demonstrate the ability of malignant B cells to release LMIF or LMIF-like factors spontaneously.