Sputum Cytokine Levels in Patients with Pulmonary Tuberculosis as Early Markers of Mycobacterial Clearance

Sputum and serum from patients with active pulmonary tuberculosis (TB), healthy purified protein derivative-positive adults, and patients with bacterial pneumonia were collected to simultaneously assess local immunity in the lungs and peripheral blood. To determine whether cytokine profiles in sputum from TB patients and control subjects were a reflection of its cellular composition, cytospin slides were prepared in parallel and assessed for the presence of relative proportions of epithelial cells, neutrophils, macrophages, and T cells. Gamma interferon (IFN-γ) in sputum from TB patients was markedly elevated over levels for both control groups. With anti-TB therapy, IFN-γ levels in sputum from TB patients decreased rapidly and by week 4 of treatment were comparable to those in sputum from controls. Further, IFN-γ levels in sputum closely followed mycobacterial clearance. Although detected at fourfold-lower levels, IFN-γ immunoreactivities in serum followed kinetics in sputum. TNF-α, interleukin 8 (IL-8) and IL-6 also were readily detected in sputum from TB patients at baseline and responded to anti-TB therapy. In contrast to IFN-γ, however, TNF-α and IL-8 levels also were elevated in sputum from pneumonia controls. These data indicate that sputum cytokines correlate with disease activity during active TB of the lung and may serve as potential early markers for sputum conversion and response to anti-TB therapy.     

Altered IL-1 Expression and Compartmentalization in Monocytes from Patients with AIDS Stimulated with Mycobacterium avium Complex

The pathophysiologic basis for the exuberant intracellular growth of Mycobacterium avium complex (MAC) in AIDS patients is unclear but may relate to altered expression of modulatory cytokines. Interleukin (IL)-1, IL-6, and TNF- expression by monocytes from AIDS patients and healthy subjects (HS) stimulated with isogeneic MAC strains (SmT, smooth-transparent, virulent; SmD, smooth-domed, avirulent) was examined. Spontaneous cytokine production was not observed in patients with AIDS. MAC strains induced less IL-1 and IL-1 release in AIDS patients than HS (P < 0.05). The ratio of cell-associated to supernatant IL-1 also was increased in AIDS patients (P = 0.03). IL-1 mRNA expression paralleled protein release in either group of subjects. In both HS and AIDS patients, stimulation with SmD induced more IL-1 and TNF- release by monocytes compared to SmT. In AIDS patients, SmD also induced greater IL-6 release than SmT (P < 0.01). Alterations in monocyte expression and compartmentalization of the regulatory cytokines IL-1 and IL-6 may enhance bacterial replication and contribute to the patho-genesis of MAC infection in AIDS.     

Type 2 Gaucher Disease with Hydrops Fetalis in an Ashkenazi Jewish Family Resulting from a Novel Recombinant Allele and a Rare Splice Junction Mutation in the Glucocerebrosidase Locus

Gaucher disease, the deficiency of the lysosomal enzyme glucocerebrosidase (EC 3.2.1.45), is frequently encountered in the Ashkenazi Jewish population. Carrier screening for Gaucher disease by enzyme analysis performed during a routine pregnancy indicated that both Ashkenazi parents were carriers. Screening for four common Gaucher mutations was subsequently performed on fetal and parental DNA. None of the common Ashkenazi mutations were identified. However, when exons 9–11 were amplified and digested withNciI to detect the L444P mutation, it appeared that the mother and the fetus had an unusual allele and that the expected paternal allele was not present. When the fetal amniocytes were found to have less than 2% of the normal glucocerebrosidase activity and a fetal sonogram revealed hydrops fetalis, the pregnancy was terminated. The diagnosis of severe type 2 Gaucher disease was confirmed at autopsy. Ultrastructural studies of epidermis from the fetus revealed the characteristic disruption of lamellar bilayers, diagnostic for type 2 Gaucher disease. In subsequent studies of the fetal DNA, long-template polymerase chain reaction amplification revealed one appropriately sized band (6.5 kb) and one smaller (5.2 kb) band. Sequencing of the 5.2-kb fragment identified a novel fusion allele resulting from recombination between the glucocerebrosidase gene and its pseudogene beginning in intron 3. This fusion allele was inherited from the father. The result was confirmed by Southern blot analysis using the enzymeSstII. Sequencing of the 6.5-kb fragment identified a previously described, although rare, T-to-G splice junction mutation in intron 10 of the maternal allele, which introduced anNciI site. The couple had a subsequent pregnancy which was also found to be affected. This case study identifies a novel recombinant allele and an unusual splice junction mutation, and demonstrates that even in the Ashkenazi population, screening for common mutations may not accurately identify the most severe forms of the disease.     

Novel FARS2 variants in patients with early onset encephalopathy with or without epilepsy associated with long survival

Mitochondrial translation is essential for the biogenesis of the mitochondrial oxidative phosphorylation system (OXPHOS) that synthesizes the bulk of ATP for the cell. Hypomorphic and loss-of-function variants in either mitochondrial DNA or in nuclear genes that encode mitochondrial translation factors can result in impaired OXPHOS biogenesis and mitochondrial diseases with variable clinical presentations. Compound heterozygous or homozygous missense and frameshift variants in the FARS2 gene, that encodes the mitochondrial phenylalanyl-tRNA synthetase, are commonly linked to either early-onset epileptic mitochondrial encephalopathy or spastic paraplegia. Here, we expand the genetic spectrum of FARS2-linked disease with three patients carrying novel compound heterozygous variants in the FARS2 gene and presenting with spastic tetraparesis, axial hypotonia and myoclonic epilepsy in two cases.Subject terms: Metabolic disorders, Mutation     

Locomotion of monocytes on endothelium is a critical step during extravasation

Monocytes, like all leukocytes, undergo a series of sequential steps during extravasation from blood into tissues: tethering, rolling, adhesion and diapedesis. We have discovered an essential step, which we call locomotion, in which the monocyte moves from a site of firm adhesion to the nearest junction to begin diapedesis. Blocking CD11a-CD18 and CD11b-CD18 on human monocytes or adhesion molecules ICAM-1 and ICAM-2 on endothelial cells prevented the monocytes from reaching junctions. The blocked monocytes spun in circles as if they were unable to direct their movement despite being able to adhere and polarize normally. This step fills a gap in the paradigm of extravasation as a multistep process.     

Wheat allergy: clinical and laboratory findings

BACKGROUND: Food allergy affects 6-8% of infants and wheat allergy is one of the common food allergies among children. The clinical and laboratory manifestations of wheat allergy were evaluated in this study. METHODS: Thirty-two children (< or =12 years old) with suspected wheat allergy were evaluated for wheat allergy. The patients underwent wheat skin prick test (SPT), measurement of wheat-specific IgE and wheat challenge test. The patients with a convincing history of anaphylaxis following ingestion of wheat or with a positive challenge test, and those with a history of immediate hypersensitivity reaction following ingestion of wheat in addition to a positive wheat SPT and/or positive wheat-specific IgE were considered wheat allergic. Then, the laboratory and clinical manifestations of their disease were studied. RESULTS: Among patients with suspected wheat allergy, 24 patients with definite wheat allergy were identified. Anaphylaxis was a dominant clinical feature, accounting for 54.1% of acute symptoms. Chronic allergy symptoms like asthma and eczema were noted in 50% of the patients. Wheat-specific IgE was higher in patients with anaphylaxis (p<0.02) and the risk of anaphylaxis was 14.4 times more in patients with wheat-specific IgE equal to or more than 3+. CONCLUSIONS: Anaphylaxis had occurred in a remarkable number of patients repeatedly, which demonstrates the severity of the reactions, poor knowledge of the disease and probable existence of more patients with mild reactions. Regarding the higher level of wheat-specific IgE in patients with anaphylaxis, wheat-specific IgE could be used to predict the severity of symptoms.     

Effects of diode low-level laser therapy on healing of tooth extraction sockets: a histopathological study in diabetic rats

Lasers in Medical Science - Diabetes mellitus is mostly interrelated to deficiency in wound healing. Low-level laser therapy has been shown to exert reliable effects on the acceleration of wound...     

Evaluating the efficacy and safety of vascular IPL for treatment of acute cutaneous leishmaniasis: a randomized controlled trial

Lasers in Medical Science - Treatment of cutaneous leishmaniasis (CL) continues to be a health concern, and alternative therapies with fewer side effects are substantially needed. This study aimed...     

How defective spermatogenesis affects sperm DNA integrity

Spermatogenesis is the essential process to maintain and promote male fertility. It is extraordinarily complex with many regulatory elements and numerous steps. The process involves several cell types, regulatory molecules, repair mechanisms and epigenetic regulators. Evidence has shown that fertility can be negatively impacted by reduced sperm DNA integrity. Sources of sperm DNA damage include replication errors and causes of DNA fragmentation which include abortive apoptosis, defective maturation and oxidative stress. This review outlines the process of spermatogenesis, spermatogonial regulation and sperm differentiation; additionally, DNA damage and currently studied DNA repair mechanisms in spermatozoon are also covered.