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Biomedical subjects

M J Robinson

Publications and source records attributed to M J Robinson.

At least 19 recordsLinked to original sources
PubMed2004

Lipopolysaccharide activation of the TPL-2/MEK/extracellular signal-regulated kinase mitogen-activated protein kinase cascade is regulated by IkappaB kinase-induced proteolysis of NF-kappaB1 p105.

The MEK kinase TPL-2 (also known as Cot) is required for lipopolysaccharide (LPS) activation of the extracellular signal-regulated kinase (ERK) mitogen-activated protein (MAP) kinase cascade in macrophages and consequent upregulation of genes involved in innate immune responses. In resting cells, TPL-2 forms a stoichiometric complex with NF-kappaB1 p105, which negatively regulates its MEK kinase activity. Here, it is shown that lipopolysaccharide (LPS) stimulation of primary macrophages causes the release of both long and short forms of TPL-2 from p105 and that TPL-2 MEK kinase activity is restricted to this p105-free pool. Activation of TPL-2, MEK, and ERK by LPS is also demonstrated to require proteasome-mediated proteolysis. p105 is known to be proteolysed by the proteasome following stimulus-induced phosphorylation of two serines in its PEST region by the IkappaB kinase (IKK) complex. Expression of a p105 point mutant, which is not susceptible to signal-induced proteolysis, in RAW264.7 macrophages impairs LPS-induced release of TPL-2 from p105 and its subsequent activation of MEK. Furthermore, expression of wild-type but not mutant p105 reconstitutes LPS stimulation of MEK and ERK phosphorylation in primary NF-kappaB1-deficient macrophages. Consistently, pharmacological blockade of IKK inhibits LPS-induced release of TPL-2 from p105 and TPL-2 activation. These data show that IKK-induced p105 proteolysis is essential for LPS activation of TPL-2, thus revealing a novel function of IKK in the regulation of the ERK MAP kinase cascade.

Animals↗
PubMed2003

Effect of a fourth Haemophilus influenzae type b immunisation in preterm infants who received dexamethasone for chronic lung disease.

AIM: To assess whether a fourth Hib polysaccharide-tetanus protein conjugate vaccine (PRP-T) would improve antibody response in preterm infants previously treated with dexamethasone for chronic lung disease. METHODS: In a pilot study 12 infants born at less than 30 weeks gestation who had received corticosteroids were given a supplementary Hib dose six weeks after completion of the primary immunisation course. Serum samples obtained before and at eight weeks following the fourth Hib dose were analysed for total level and avidity of anti-PRP antibody. RESULTS: There was no significant increase in the geometric mean titre (GMT) of anti-PRP antibody resulting from the fourth Hib immunisation (GMT: pre 2.35 micro g/ml, post 2.24 micro g/ml, p = 0.79). A subgroup of six infants had subprotective antibody levels (<1.0 micro g/ml) after the primary immunisation course, which remained subprotective following the extra Hib immunisation. Despite the poor response in total antibody level, the study group showed a significant rise in PRP specific IgG avidity following the fourth immunisation (GMAI: pre 0.076, post 0.138, p = 0.043). CONCLUSION: An additional Hib immunisation given to recently steroid treated preterm infants six weeks after completion of the primary schedule did not augment primary immunogenicity. However, increasing avidity may imply successful priming and long term immunity to Hib.

Antibodies, Viral↗
PubMed2001

Sonographic appearance of aggressive angiomyxoma of the scrotum.

Aggressive angiomyxoma (AAM) is a rare, locally infiltrative tumor that occurs almost exclusively in the pelvic and perineal regions of women of childbearing age. We report the unusual case of a 26-year-old man with an AAM presenting as a slowly enlarging scrotal mass. Gray-scale scrotal sonography demonstrated a well-demarcated, hypoechoic, extratesticular, extraepididymal mass with multiple thin, echogenic internal septa. The mass arose inferior to the left testicle and displaced the testicle cephalad. Color Doppler sonography revealed surrounding vascularity but no Doppler signals within the mass. The testicles and epididymides demonstrated normal echogenicity and vascularity. Histologic examination of the excised mass revealed a well-demarcated, nonencapsulated lesion composed of spindle-shaped cells in a myxoid background with a prominent vascular component.

Adult↗
PubMed2001

Extranodal lymphoplasmacytoid lymphoma (immunocytoma) presenting as small intestinal obstruction.

A 57-year-old woman presented with intermittent symptoms of intestinal obstruction. Workup provided nondiagnostic radiologic studies. An exploratory laparotomy revealed a segmental dilatation in the proximal ileum, which showed diffuse thickening of the intestinal wall. Microscopic examination of the affected area disclosed a diffuse transmural infiltrate composed of small lymphocytes, mature plasma cells, and lymphoplasmacytoid cells in different stages of maturation associated with extracellular periodic acid-Schiff-positive material. In addition, serum protein electrophoresis showed a monoclonal immunoglobulin M kappa paraprotein. Postoperative workup did not demonstrate evidence of systemic involvement. The morphologic features and immunohistochemical and molecular analyses were consistent with lymphoplasmacytoid lymphoma (immunocytoma). We report an unusual case of primary extranodal immunocytoma involving the small intestine and discuss its clinicopathologic features.

Female↗
PubMed2001

Ceroid histiocytosis: an unusual cause of atraumatic splenic rupture.

A rare case of atraumatic splenic rupture due to ceroid histiocytosis is described in a 56-year-old man. During hospitalization, he complained of epigastric pain, which was not associated with nausea or vomiting. Hematologic indices showed steadily declining hemoglobin, and subsequent radiologic imaging revealed massive splenomegaly. An exploratory laparotomy revealed hemoperitoneum associated with a subcapsular splenic rupture. Splenic pathology showed numerous ceroid-containing histiocytes. We believe this to be the fourth reported case in the English language of atraumatic splenic rupture due to ceroid histiocytosis.

Alcoholism↗
PubMed2000

Stress pathway activation induces phosphorylation of retinoid X receptor.

Cellular stresses inhibit retinoid signaling, but the molecular basis for this phenomenon has not been revealed. Here, we present evidence that retinoid X receptor (RXR) is a substrate for both mitogen-activated protein kinase kinase-4 (MKK4/SEK1) and its downstream mediator c-Jun N-terminal kinase (JNK). MKK4/SEK1 and JNK recognized distinct features on RXR in the DE and AB regions, respectively. Phosphorylation by MKK4/SEK1 had profound effects on the biochemical properties of RXR, inhibiting the expression of genes activated by RXR-retinoic acid receptor complexes. Tyr-249 in the RXR DE region was required for the inhibitory effect of MKK4/SEK1. These effects were significantly reduced in MKK4/SEK1-null cells, indicating that MKK4/SEK1 is required for the suppression of retinoid signaling by stress. Findings presented here demonstrate that MKK4/SEK1 can directly modulate transcription by phosphorylating RXR, a novel MKK4/SEK1 substrate.

Animals↗
PubMed2000

A comparison of human S100A12 with MRP-14 (S100A9).

MRP-8 and -14 are two S100 proteins highly expressed as a complex by neutrophils, and to a lesser extent by monocytes and certain squamous epithelia. However, less is known about the close homologue S100A12. This S100 protein is expressed by neutrophils and here we show that it is also expressed by monocytes, but not lymphocytes. An absence of coimmunoprecipitation of MRP-14 and S100A12 indicates that S100A12 is not associated with the MRP proteins in vivo. When directly compared to MRP-14, S100A12 expression by squamous epithelia is more restricted. In esophagus and psoriatic skin, S100A12 is differentially regulated, like MRP-14, but the expression pattern of the two S100 proteins is quite different.

Antibodies↗
PubMed2000

The use of psychotropics in the medically ill.

Underlying medical illness may present a challenge when prescribing psychotropic medications. Disease-related changes in pharmacokinetics and pharmacodynamics, as well as vulnerability to side effects, polypharmacy, and potential drug interactions are all important considerations. Successful treatment of psychiatric disorders may have a beneficial impact on medical morbidity and mortality, as well as quality of life. This article reviews the relevant considerations when using psychotropic medications in six major medical populations (cardiac, cerebral vascular, pulmonary, liver, renal, and seizure disorders).

Drug Interactions↗
PubMed2000

Chordoid glioma: a novel tumor of the third ventricle.

Chordoid glioma of the third ventricle is a recently characterized primary neoplasm of the central nervous system. We present a case and discuss the pathologic and radiologic features. We are aware of only 16 other cases documented in the world literature. This radiologic-pathologic correlation alerts pathologists and radiologists to recognize chordoid glioma as a distinct clinicopathologic entity restricted to the third ventricular area of adult patients.

Adult↗