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Biomedical subjects

Sheraz Yaqub

Publications and source records attributed to Sheraz Yaqub.

9 recordsLinked to original sources

FOXP3+CD4+CD25+ adaptive regulatory T cells express cyclooxygenase-2 and suppress effector T cells by a prostaglandin E2-dependent mechanism.

CD4+CD25+ regulatory T (T(R)) cells suppress effector T cells by partly unknown mechanisms. In this study, we describe a population of human suppressive CD4+CD25+ adaptive T(R) (T(R)(adapt)) cells induced in vitro that express cyclooxygenase 2 (COX-2) and the transcription factor FOXP3. T(R)(adapt) cells produce PGE(2) and suppress effector T cell responses in a manner that is reversed by COX inhibitors and PGE(2) receptor-specific antagonists. In resting CD4+CD25- T cells, treatment with PGE(2) induced FOXP3 expression. Thus, autocrine and paracrine effects of PGE(2) produced by COX-2-positive T(R)(adapt) cells may be responsible for both the FOXP3+ phenotype and the mechanism used by these cells to suppress effector T cells.

Cell Communication↗

[Bite wound infections].

BACKGROUND: The lifetime risk of experiencing a bite wound, human or animal, is approximately 50%, and bite wounds account for approximately 1% of all visits to emergency departments. The majority of bite wounds are inflicted by dogs and cats. MATERIAL AND METHODS: A review of the literature on the diagnosis and treatment of bite wound infections is presented. RESULTS: The most common pathogens associated with bite wounds are Streptococcus species, Staphylococcus species, Pasteurella multocida, Capnocytophaga canimorsus and anaerobic bacteria. Sporadically other pathogens are isolated from bite wounds. Human bites differ from animal bites by higher prevalence of Staphylococcus aureus and Eikenella corrodens. INTERPRETATION: It is important to be aware of the possibility of complicating infections following bite wounds, particularly after cat bites. Phenoxymethyl penicillin should be the drug of choice in treatment of infections associated with cat and dog bites. However, in case of slow recovery or no improvement, simultaneous lymphadenopathy or pneumonia, S. aureus or Francisella tularensis should be suspected; ciprofloxacin is recommended. For human bite infections the recommend treatment is phenoxymethyl penicillin in combination with penicillinase-stable penicillin.

Animals↗

[Tularemia from a cat bite].

We report the first case in Norway of a man who developed ulceroglandular tularaemia following a cat bite. If after feline contact, patients develop skin and soft-tissue infections that fail to respond to therapy with penicillin, physicians should consider the possibility of tularaemia. Our patient was successfully treated with ciprofloxacin, which is effective against Francisella tularensis and most pathogens associated with feline infections. A greater awareness of infections following a cat bite is important for recognising this uncommon condition.

Animals↗

[Acute visual loss in an eight-year-old girl].

BACKGROUND: There are many causes of acute visual loss in childhood. Inflammation of the optic nerve, optic neuritis, is rare. While mostly unilateral in adults, the disease often presents bilaterally in childhood. Furthermore, progression to demyelinating disease is unusual and optic neuritis has a better prognosis in childhood than in adulthood. MATERIAL AND METHODS: We describe an 8-year-old girl who over a few days developed painful eyes and profound visual loss. She had afferent pupil defect; ophthalmoscopy showed bilateral papilloedema, characteristic of bilateral optic neuritis. Current literature and guidelines are reviewed with regards to diagnosis and treatment of optic neuritis in childhood. RESULTS: Steroids seem to be beneficial in the treatment of optic neuritis in childhood. Following five days intravenous administration of methylprednisolone and an oral taper over five weeks, visual acuity was almost normalised in both eyes. INTERPRETATION: After studying the literature, we started a treatment with good outcome. Although the prognosis is usually good in children even without treatment, it is important to be aware that there are cases in which treatment with steroids is recommended.

Acute Disease↗

Severe, reversible pulmonary hypertension in a patient with monoclonal gammopathy and features of dermatomyositis.

Pulmonary hypertension is an extremely serious and potentially fatal disorder. Although pulmonary hypertension is a potential complication of connective tissue disease, it has been reported rarely in patients with dermatomyositis. Similarly, multiple myeloma is rare in patients with dermatomyositis. We describe a patient with severe pulmonary hypertension who also had features of dermatomyositis and monoclonal gammopathy. To our knowledge, this is the first reported case of a patient in whom all 3 disorders occurred concurrently. Even more striking is the fact that the patient responded to treatment with cyclophosphamide and prostacyclin. He is asymptomatic more than 5 years after treatment was discontinued.

Adult↗

Activation of C-terminal Src kinase (Csk) by phosphorylation at serine-364 depends on the Csk-Src homology 3 domain.

In the present study, we investigate the mechanism for the protein kinase A (PKA)-mediated activation of C-terminal Src kinase (Csk). Although isolated Csk kinase domain was phosphorylated at Ser(364) by PKA to the same stoichiometry as wild-type Csk, significant activation of the isolated Csk kinase domain by PKA was observed only in the presence of the purified Src homology 3 domain (SH3 domain). Furthermore, the interaction between the SH3 and kinase domains was facilitated by PKA-mediated phosphorylation of the kinase domain, as evaluated by surface plasmon resonance. This suggests that an overall structural domain organization and interaction between the kinase and SH3 domains are important for the activity of Csk and its regulation by PKA.

CSK Tyrosine-Protein Kinase↗

A human whole blood model of LPS-mediated suppression of T cell activation.

BACKGROUND: Lipopolysaccharide (LPS) is the main initiator of the early signaling events leading to sepsis caused by Gram-negative bacteria. Late stages of sepsis are associated with impairments of T lymphocyte function, a condition associated with nosocomial infection and poor outcome. The molecular basis for septic immunosuppression is not fully understood. MATERIAL/METHODS: Human whole blood was incubated ex vivo with purified LPS. Cytokine responses and T cell proliferation were assessed, and the role of cyclic 3',5'-adenosine monophosphate (cAMP) in T cell suppression by LPS was studied using a cAMP-antagonist (Rp-8-Br-cAMPS). RESULTS: Adding LPS (0.01 to 10 microg/ml) to human blood ex vivo caused a release of prostaglandin E2 (PGE2) in a concentration- and time-dependent manner, with maximal levels of PGE2 obtained with 10 microg LPS per ml blood after 10 hours of incubation. Adding PGE2-concentrations ranging from 0.03 to 10 microM to purified T cells completely abrogated T cell activation and proliferative response, which was largely reversed by adding Rp-8-Br-cAMPS. Peripheral blood mononuclear cells (PBMC) and T cells harvested from whole blood cultured in the presence of LPS ex vivo showed attenuated proliferative response (30-70%) (purified T cells and PBMC) and reduced IL-2 production (85%) upon T cell receptor (TCR)/CD3 activation with anti-CD3. The proliferation in T cells and PBMC was in part restored by Rp-8-Br-cAMPS. CONCLUSIONS: The human whole blood model of LPS-mediated T lymphocyte suppression described in this paper is time and cost efficient, as well as easy to use.

8-Bromo Cyclic Adenosine Monophosphate↗

[Smoking ban in psychiatric department].

BACKGROUND: It is well known that nicotine and caffeine can increase tension and anxiety, disturb sleep and cause a variety of smoking related health problems. MATERIAL AND METHODS: On 1 March 2001, it was decided to ban smoking in a general psychiatric inpatient unit and the patients were asked to confine smoking to outdoor areas. In a retrospective study we looked at the effects of the ban on smoking on "as needed" medication, ward atmosphere and incidents related to the change. The records from 30 patients discharged before the ban and 30 patients after the ban were examined and the demands for "as needed" medication registered. RESULTS: Two-sample t-test analyses of the groups showed a significant difference in "as needed" medications used between the two groups, with a reduction in the group discharged after the smoking ban (p < 0.01). There was a substantially reduction in coffee consumption and positive improvement in ward atmosphere after the ban as observed by the staff. INTERPRETATION: The material is limited; others are encouraged to proceed with validation of our experience.

Adult↗

Molecular mechanisms for protein kinase A-mediated modulation of immune function.

Protein kinase A (PKA) is a serine/threonine kinase that regulates a number of cellular processes important for immune activation and control. Modulation of signal transduction by PKA is a complex and diverse process, and differential isozyme expression, holoenzyme composition and subcellular localization contribute specificity to the PKA signalling pathway. In lymphocytes, phosphorylation by PKA has been demonstrated to regulate antigen receptor-induced signalling both by altering protein-protein interactions and by changing the enzymatic activity of target proteins. PKA substrates involved in immune activation include transcription factors, members of the MAP kinase pathway and phospholipases. The ability of PKA type I to regulate activation of signalling components important for formation of the immunological synapse, demonstrates that the cAMP signalling pathway can directly modulate proximal events in lymphocyte activation. Furthermore, the recent discovery that PKA regulates Src kinases through modulation of Csk, supports the notion that PKA is involved in the fine-tuning of immune receptor signalling in lipid rafts.

CSK Tyrosine-Protein Kinase↗