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M Turner

Publications and source records attributed to M Turner.

At least 127 records · Page 7Linked to original sources
PubMed1997

Syk tyrosine kinase is required for the positive selection of immature B cells into the recirculating B cell pool.

The tyrosine kinase Syk has been implicated as a key signal transducer from the B cell antigen receptor (BCR). We show here that mutation of the Syk gene completely blocks the maturation of immature B cells into recirculating cells and stops their entry into B cell follicles. Furthermore, using radiation chimeras we demonstrate that this developmental block is due to the absence of Syk in the B cells themselves. Syk-deficient B cells are shown to have the life span of normal immature B cells. If this is extended by over-expression of Bcl-2, they accumulate in the T zone and red pulp of the spleen in increased numbers, but still fail to mature to become recirculating follicular B cells. Despite this defect in maturation, Syk-deficient B cells were seen to give rise to switched as well as nonswitched splenic plasma cells. Normally only a proportion of immature B cells is recruited into the recirculating pool. Our results suggest that Syk transduces a BCR signal that is absolutely required for the positive selection of immature B cells into the recirculating B cell pool.

Animals↗
PubMed1997

Syk and Fyn are required by mouse megakaryocytes for the rise in intracellular calcium induced by a collagen-related peptide.

Stimulation of platelets by collagen leads to activation of a tyrosine kinase cascade resulting in secretion and aggregation. We have recently shown that this pathway involves rapid tyrosine phosphorylation of an Fc receptor gamma chain, which contains an immunoreceptor tyrosine-based activation motif (ITAM), enabling interaction with the tandem SH2 domains of the tyrosine kinase Syk. Activation of Syk lies upstream of tyrosine phosphorylation of phospholipase Cgamma2. In the present study we sought to test directly the role of the ITAM/Syk interaction and the role of the Src-related kinases in collagen receptor signaling using mouse megakaryocytes. We demonstrate that the calcium-mobilizing action of a collagen-related peptide (CRP) is kinase-dependent, inhibited by the microinjection of the tandem SH2 domains of Syk and abolished in Syk-deficient mice. Furthermore, the CRP response is abolished by the Src family kinase inhibitor PP1 and inhibited in Fyn-deficient mice. In contrast, the calcium response to the G-protein-linked receptor agonist thrombin is not significantly altered under these conditions. These results provide direct evidence of the functional importance of Fyn and Syk in collagen receptor signaling and support the megakaryocyte as a model for the study of proteins involved in this pathway.

Animals↗
PubMed1997

A critical role for Syk in signal transduction and phagocytosis mediated by Fcgamma receptors on macrophages.

Receptors on macrophages for the Fc region of IgG (FcgammaR) mediate a number of responses important for host immunity. Signaling events necessary for these responses are likely initiated by the activation of Src-family and Syk-family tyrosine kinases after FcgammaR cross-linking. Macrophages derived from Syk-deficient (Syk-) mice were defective in phagocytosis of particles bound by FcgammaRs, as well as in many FcgammaR-induced signaling events, including tyrosine phosphorylation of a number of cellular substrates and activation of MAP kinases. In contrast, Syk- macrophages exhibited normal responses to another potent macrophage stimulus, lipopolysaccharide. Phagocytosis of latex beads and Escherichia coli bacteria was also not affected. Syk- macrophages exhibited formation of polymerized actin structures opposing particles bound to the cells by FcgammaRs (actin cups), but failed to proceed to internalization. Interestingly, inhibitors of phosphatidylinositol 3-kinase also blocked FcgammaR-mediated phagocytosis at this stage. Thus, PI 3-kinase may participate in a Syk-dependent signaling pathway critical for FcgammaR-mediated phagocytosis. Macrophages derived from mice deficient for the three members of the Src-family of kinases expressed in these cells, Hck, Fgr, and Lyn, exhibited poor Syk activation upon FcgammaR engagement, accompanied by a delay in FcgammaR-mediated phagocytosis. These observations demonstrate that Syk is critical for FcgammaR-mediated phagocytosis, as well as for signal transduction in macrophages. Additionally, our findings provide evidence to support a model of sequential tyrosine kinase activation by FcgammaR's analogous to models of signaling by the B and T cell antigen receptors.

Androstadienes↗
PubMed1997

New variant Creutzfeldt-Jakob disease: psychiatric features.

BACKGROUND: An apparently new variant of Creutzfeldt-Jakob disease (CJD), new variant CJD (nvCJD), was identified in the UK in 1996. There have now been 21 cases of nvCJD in the UK and one in France. Psychiatric symptoms are prominent in the initial presentation in these cases. METHODS: Cases of nvCJD are identified mainly by direct referral from neurologists and neuropathologists. Detailed clinical information was obtained by review of case notes and interviewing patients' relatives. We report the psychiatric features of the first 14 cases on nvCJD in the UK. Psychiatric notes were examined in all 13 of these cases who were seen by a psychiatrist. RESULTS: Eight cases were women. All 14 cases had early psychiatric features and in nine, the first symptom was psychiatric. 13 cases were seen by a psychiatrist and the majority were diagnosed as suffering from depression or depression secondary to organic disease. Two cases suffered from first-rank symptoms suggestive of psychotic illness and transient delusions and auditory or visual hallucinations occurred in the majority. All cases were referred to a neurologist as the illness evolved and neurological signs developed. INTERPRETATION: Psychiatric symptoms are a consistent early clinical feature in nvCJD. Analysis of the psychiatric symptoms does not suggest specific features that readily allow distinction from more common psychiatric disorders, although the occurrence of associated persistent sensory symptoms may raise the possibility of this diagnosis. Neurological signs, including ataxia, involuntary movements and cognitive impairment developed in all cases and the evolution of increasing neurological deficits is likely to remain critical to the clinical diagnosis of nvCJD.

Adult↗
PubMed1997

Long-term hospitalization for tuberculosis control. Experience with a medical-psychosocial inpatient unit.

CONTEXT: Patients with tuberculosis (TB) who are nonadherent to therapy or have complicated medical or social problems pose a threat to public health. In some cases, hospitalization may be a necessary component of a comprehensive TB control program. OBJECTIVE: To describe experience with a new inpatient program for TB control. DESIGN: Retrospective review. SETTING: Eighteen-bed, secure, TB treatment unit in a state public health hospital providing a spectrum of acute and chronic care services. PATIENTS: Patients with known or suspected TB who were unable to be treated as outpatients and were hospitalized from 1990 through 1995. INTERVENTIONS: Voluntary or involuntary hospitalization, with medical, psychosocial, and legal services. MAIN OUTCOME MEASURES: Admissions, treatment completion, and disposition. RESULTS: A total of 166 patients with a confirmed diagnosis of TB accounted for 214 hospitalizations for TB. The mean age was 42 years, 132 (79.5%) were men, 84 (50.6%) were nonwhite, and 45 (27.1%) were foreign born. At the time of admission, 58 patients (34.5%) were homeless, 116 (69.9%) had a history of abuse of alcohol or other drugs, and 46 (31.7%) were positive for human immunodeficiency virus. The mean length of stay was 119.7 days (median, 70 days; range, 7-656 days), and was higher among homeless patients than nonhomeless patients (168.8 vs 93.4 days). Of 48 patients (28.9%) who were admitted involuntarily, 21 required long-term confinement under court order. Admission indications (not mutually exclusive) changed over 5 years: nonadherence decreased (95% to 34%), medical complexity increased (14% to 77%), short-term isolation increased (19% to 39%), and involuntary admission decreased (54% to 13%). Of 157 patients with positive cultures for Mycobacterium tuberculosis, 36 (23.1%) were resistant to at least 1 drug, including 16 who were multidrug resistant. A total of 123 patients (74.7%) were discharged to an outpatient setting to complete therapy, 40 (24.1%) required inpatient care to complete therapy, and 3 died (1 from TB) before discharge. CONCLUSIONS: A high proportion of patients with TB who failed outpatient therapy completed treatment in a combined medical and psychosocial inpatient unit. During the 5-year study period, involuntary admissions decreased and most patients completed therapy as outpatients. In Massachusetts, this program plays an important role in protecting public health and in providing specialized medical management for patients to complete therapy in a safe and supportive environment.

Adult↗
PubMed1997

The Fc receptor gamma-chain and the tyrosine kinase Syk are essential for activation of mouse platelets by collagen.

Activation of mouse platelets by collagen is associated with tyrosine phosphorylation of multiple proteins including the Fc receptor gamma-chain, the tyrosine kinase Syk and phospholipase Cgamma2, suggesting that collagen signals in a manner similar to that of immune receptors. This hypothesis has been tested using platelets from mice lacking the Fc receptor gamma-chain or Syk. Tyrosine phosphorylation of Syk and phospholipase Cgamma2 by collagen stimulation is absent in mice lacking the Fc receptor gamma-chain. Tyrosine phosphorylation of phospholipase Cgamma2 by collagen stimulation is also absent in mice platelets which lack Syk, although phosphorylation of the Fc receptor gamma-chain is maintained. In contrast, tyrosine phosphorylation of platelet proteins by the G protein-coupled receptor agonist thrombin is maintained in mouse platelets deficient in Fc receptor gamma-chain or Syk. The absence of Fc receptor gamma-chain or Syk is accompanied by a loss of secretion and aggregation responses in collagen- but not thrombin-stimulated platelets. These observations provide the first direct evidence of an essential role for the immunoreceptor tyrosine-based activation motif (ITAM) in signalling by a non-immune receptor stimulus.

Animals↗
PubMed1997

Simultaneous genotyping for all three known structural mutations in the human mannose-binding lectin gene.

We describe a rapid and simple method for genotyping the three known structural mutations within exon 1 of the mannan-binding lectin (MBL) gene. A PCR-amplifiable synthetic DNA (Universal Heteroduplex Generator) was annealed to genomic PCR product from exon 1 to generate unique DNA heteroduplexes for each mutation. Heteroduplexes were then resolved by non-denaturing polyacrylamide gel electrophoresis. The technique was initially validated with previously typed samples and then applied to previously untyped samples with the results confirmed by DNA sequencing.

Amino Acid Sequence↗
PubMed1997

A requirement for the Rho-family GTP exchange factor Vav in positive and negative selection of thymocytes.

The T cell repertoire is shaped by positive and negative selection of thymocytes that express low levels of T cell receptor (TCR) and both CD4 and CD8. TCR-mediated signals that determine these selection processes are only partly understood. Vav, a GDP-GTP exchange factor for Rho-family proteins, is tyrosine phosphorylated following TCR stimulation, suggesting that it may transduce TCR signals. We now demonstrate that mice lacking Vav are viable and display a profound defect in the positive selection of both class I- and class II-restricted T cells. In contrast, Vav is not essential for negative selection, though in its absence negative selection is much less effective. Vav may influence the efficiency of TCR-induced selection events by regulating the intracellular calcium flux of thymocytes.

Animals↗
PubMed1997

Transient leukaemia cutis in chronic lymphocytic leukaemia.

Leukaemia cutis arises due to cutaneous infiltration of neoplastic leukocytes or their precursors. Recent evidence suggests that this sign does not necessarily herald a poor prognosis. We describe a 72-year-old woman with B-cell chronic lymphatic leukaemia (CLL) who developed a papular eruption on her breast at the site of a recent herpetic eruption. Histology and immunostaining showed a dense dermal B-cell infiltrate in keeping with leukaemia cutis. The papules cleared in 6 months without treatment, leaving atrophic scars. The histological features and possible aetiological mechanisms of post-herpetic papular eruptions in CLL are reviewed.

Aged↗
PubMed1997

Transient leukaemia cutis in chronic lymphocytic leukaemia.

Leukaemia cutis arises from cutaneous infiltration by neoplastic leukocytes or their precursors. Recent evidence suggests that this sign does not necessarily herald a poor prognosis. We describe a 72-year-old woman with B-cell chronic lymphatic leukaemia who developed a papular eruption of her breast at the site of a recent herpetic eruption. Histology and immunostaining showed a dense dermal B-cell infiltrate in keeping with leukaemia cutis. The papules cleared in 6 months without treatment, leaving atrophic scars. The histological features and possible aetiological mechanisms of post-herpetic papular eruptions in chronic lymphatic leukaemia are reviewed.

Aged↗
PubMed1997

Ploidy profile of morphologically normal squamous epithelium adjacent to high grade cervical intraepithelial neoplasia.

We have investigated the ploidy profile of morphologically normal mucosa adjacent to high grade CIN (n = 16) and also from normal cervix (n = 18). DNA ploidy was assessed using flow cytometry and image analysis. All cases were diploid by both modalities. Our results show that morphologically normal squamous mucosa has a stable ploidy profile even when it lies adjacent to high grade CIN. This finding supports the view that high grade CIN is a neoplastic expansion of transformed cells rather than the result of a field change effect.

Epithelium↗
PubMed1997

Spontaneously hypertensive rat Y chromosome increases indexes of sympathetic nervous system activity.

Previous studies from our laboratory have demonstrated that the Y chromosome from the spontaneously hypertensive rat (SHR) is responsible for a significant portion of the elevated blood pressure and also produces an earlier pubertal rise in plasma testosterone. We performed the following studies to determine whether the SHR Y chromosome raises blood pressure by sympathetic nervous system responses as measured by adrenal chromogranin A and plasma and tissue catecholamines. Male SHR from the University of Akron colony were studied from 5 to 20 weeks of age. Blood pressure was measured by tail-cuff, tail artery cannulation, and aortic telemetry (Data Sciences); acute (air stress) and chronic (territorial colony) social stressors were compared; blood was collected for determination of plasma catecholamines; and adrenal glands were analyzed at 15 weeks for catecholamines. Rats with the SHR Y chromosome had higher blood pressure and plasma norepinephrine than those with the normotensive Wistar-Kyoto (WKY) Y chromosome. However, the SHR Y chromosome did not significantly change responsiveness to acute or chronic stressors. Phentolamine and clonidine prevented the stress responses. Adrenal chromogranin A levels were elevated 37% and 40% and adrenal norepinephrine content 29% and 100% at 4 and 10 weeks of age, respectively, in rats with an SHR Y chromosome compared with WKY. Chemical sympathectomy normalized blood pressure in all strains and significantly reduced norepinephrine (36% to 41%) in all strains except in WKY, which already had a normal blood pressure. In conclusion, the SHR Y chromosome appears to increase the chronic sympathetic nervous system. A potential mechanism could be a Y locus that influences chronic sympathetic nervous system activity, which may reinforce neurohumoral factors and structural components of the vessel wall, accelerating the development of hypertension.

Adrenal Glands↗
PubMed1997

Malingering.

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Antisocial Personality Disorder↗
PubMed1997

Postnatal depression and elation among mothers and their partners: prevalence and predictors.

BACKGROUND: Correlates and predictors of mood disturbances at 3 days and 6 weeks postpartum were assessed in Irish mothers and their partners. METHOD: The Edinburgh Postnatal Depression Scale (EPDS) and the Highs Scale were used to assess 370 mothers and their partners. Socio-demographic, clinical and obstetric data were collected at patients' first antenatal visit. Factors associated with EPDS scores of > or = 13 and Highs score of > or = 8 were examined. RESULTS: On the EPDS 11.4% of mothers scored > or = 13 at 3 days postpartum and 11% at 6 weeks, while 18.3% of mothers scored > or = 8 on the Highs Scale at 3 days and 9% at 6 weeks. Scores on the EPDS and Highs Scale were interrelated. Factors associated with EPDS scores of > or = 13 at 6 weeks were single status, unemployment, unplanned pregnancy, public status and bottlefeeding. The best predictors of EPDS > or = 13 at 6 weeks were mothers' scores on the EPDS and the Highs Scale at 3 days. Three per cent of partners scored > or = 13 on the EPDS at 3 days postpartum and 1.2% at 6 weeks. CONCLUSIONS: Factors associated with mothers' mood disturbance were readily identifiable and collected routinely at antenatal intake. Mothers' mood within 3 days of delivery was the best predictor of later postnatal depression. Paternal mood disturbance was rare. Certain women may be at increased risk for postnatal mood disturbance and may be amenable to early identification and intervention.

Bipolar Disorder↗