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At least 901 records · Page 50Linked to original sources
PubMed2005

Neutrophils lacking platelet-endothelial cell adhesion molecule-1 exhibit loss of directionality and motility in CXCR2-mediated chemotaxis.

Time-lapsed videomicroscopy was used to study the migration of platelet-endothelial cell adhesion molecule-1-deficient (PECAM-1(-/-)) murine neutrophils undergoing chemotaxis in Zigmond chambers containing IL-8, KC, or fMLP gradients. PECAM-1(-/-) neutrophils failed to translocate up the IL-8, KC, and fMLP gradients. Significant reductions in cell motility and cell spreading were also observed in IL-8 or KC gradients. In wild-type neutrophils, PECAM-1 and F-actin were colocalized at the leading fronts of polarized cells toward the gradient. In contrast, in PECAM-1(-/-) neutrophils, although F-actin also localized to the leading front of migrating cells, F-actin polymerization was unstable, and cycling was remarkably increased compared with that of wild-type neutrophils. This may be due to the decreased cytokine-induced mobilization of the actin-binding protein, moesin, into the cytoskeleton of PECAM-1(-/-) neutrophils. PECAM-1(-/-) neutrophils also exhibited intracellularly dislocalized Src homology 2 domain containing phosphatase 1 (SHP-1) and had less IL-8-induced SHP-1 phosphatase activity. These results suggest that PECAM-1 regulates neutrophil chemotaxis by modulating cell motility and directionality, in part through its effects on SHP-1 localization and activation.

Actins↗
PubMed1999

Gab-family adapter proteins act downstream of cytokine and growth factor receptors and T- and B-cell antigen receptors.

We previously found that the adapter protein Gab1 (110 kD) is tyrosine-phosphorylated and forms a complex with SHP-2 and PI-3 kinase upon stimulation through either the interleukin-3 receptor (IL-3R) or gp130, the common receptor subunit of IL-6-family cytokines. In this report, we identified another adapter molecule (100 kD) interacting with SHP-2 and PI-3 kinase in response to various stimuli. The molecule displays striking homology to Gab1 at the amino acid level; thus, we named it Gab2. It contains a PH domain, proline-rich sequences, and tyrosine residues that bind to SH2 domains when they are phosphorylated. Gab1 is phosphorylated on tyrosine upon stimulation through the thrombopoietin receptor (TPOR), stem cell factor receptor (SCFR), and T-cell and B-cell antigen receptors (TCR and BCR, respectively), in addition to IL-3R and gp130. Tyrosine phosphorylation of Gab2 was induced by stimulation through gp130, IL-2R, IL-3R, TPOR, SCFR, and TCR. Gab1 and Gab2 were shown to be substrates for SHP-2 in vitro. Overexpression of Gab2 enhanced the gp130 or Src-related kinases-mediated ERK2 activation as that of Gab1 did. These data indicate that Gab-family molecules act as adapters for transmitting various signals.

Adaptor Proteins, Signal Transducing↗
PubMed1999

[Usefulness of 67Ga scintigraphy in deciding surgical indication in secondary hyperparathyroidism].

In order to evaluate the usefulness in deciding surgical indication in secondary hyperparathyroidism (SHP), 67Ga scintigraphy was performed in 37 patients of SHP before parathyroidectomy (PTx). The radionuclide accumulation in skull and submandible was classified into 4 patterns (skull-submandibular pattern, skull pattern, submandibular pattern and normal pattern). Serum alkaline phosphatase levels were significantly elevated in patients of skull-submandibular pattern (13 cases) compared with skull pattern (6 cases), submandibular pattern (6 cases) and normal pattern (12 cases). Serum intact parathyroid hormone levels were significantly elevated in patients of skull-submandibular and skull patterns compared with normal pattern. No significant difference was observed among the weight of resected parathyroid glands. In 4 of 6 patients of normal pattern on 67Ga scintigram, bone scintigraphy showed a characteristic pattern of SHP including an increased accumulation in the skull and submandible. Bone mineral density (BMD) in the distal radius was increased within six to twelve months after PTx in 10 of 11 patients of skull-submandibular pattern on 67Ga scintigram, whereas only one patient showed an increase in BMD in 9 patients of normal pattern. In summary, it was concluded that 67Ga scintigraphy could provide a useful information in deciding the indication for PTx in secondary hyperparathyroidism.

Citrates↗
PubMed1999

[Long-term development of children with Schönlein-Henoch purpura associated with anti-neutrophil cytoplasmic antibodies].

OBJECTIVE: The purpose of this study was to assess the frequency of antineutrophil cytoplamic antibodies (ANCA) in Schönlein-Henoch purpura (SHP) and its long-term significance. PATIENTS AND METHODS: IgG and IgA classes of ANCA were studied by indirect immunofluorescence (IIF) and IgG-ANCA against myeloperoxidase (MPO) and against proteinase-3 (PR-3) were determined by ELISA in 50 children with SHP. Eight (16%) of the patients had renal involvement during the acute phase, but none had a permanent nephropathy after a 7-17 year follow-up. RESULTS: Positive IgG ANCA were found in 5 (10%) of the cases and only one of these children also had IgA ANCA. The ELISA against MPO and P-3 was negative in all patients. None of the 5 patients with ANCA showed nephropathy during the acute phase nor relapses or permanent nephropathy. CONCLUSIONS: A minority of children with SHP are positive for ANCA and, in the absence of nephropathy, this is not associated with a bad long-term prognosis.

Acute Disease↗
PubMed2001

Maturation of erythroid cells and erythroleukemia development are affected by the kinase activity of Lyn.

This study examined the impact of the tyrosine kinase Lyn on erythropoietin-induced intracellular signaling in erythroid cells. In J2E erythroleukemic cells, Lyn coimmunoprecipitated with numerous proteins, including SHP-1, SHP-2, ras-GTPase-activating protein, signal transducers and activators of transcription (STAT) 5a, STAT5b, and mitogen-activated protein kinase; however, introduction of a dominant-negative Lyn (Y397F Lyn) inhibited the interaction of Lyn with all of these molecules except SHP-1. Cells containing the dominant-negative Lyn displayed altered intracellular phosphorylation patterns, including mitogen-actiated protein kinase, but not erythropoietin receptor, Janus-activated kinase (JAK) 2, or STAT5. As a consequence, erythropoietin-initiated differentiation and basal proliferation were severely impaired. Y397F Lyn reduced the protein levels of erythroid transcription factors erythroid Kruppel-like factor and GATA-1 up to 90%, which accounts for the inability of J2E cells expressing Y397F Lyn to synthesize hemoglobin. Although Lyn was shown to bind several sites on the cytoplasmic domain of the erythropoietin receptor, it was not activated when a receptor mutated at the JAK2 binding site was ectopically expressed in J2E cells indicating that JAK2 is the primary kinase in erythropoietin signaling and that Lyn is a secondary kinase. In normal erythroid progenitors, erythropoietin enhanced phosphorylation of Lyn; moreover, exogenous Lyn increased colony forming unit-erythroid, but not burst forming uniterythroid, colonies from normal progenitors, demonstrating a stage-specific effect of the kinase. Significantly, altering Lyn activity in J2E cells had a profound effect on the development of erythroleukemias in vivo: the mortality rate was markedly reduced and latent period extended when either wild-type Lyn or Y397F Lyn was introduced into these cells. Taken together, these data show that Lyn plays an important role in intracellular signaling in nontransformed and leukemic erythroid cells.

Amino Acid Sequence↗
PubMed2001

No involvement of Erk/MAP kinases in IL-6-induced proliferation of a B cell hybridoma cell line.

Interleukin-6 (IL-6) is a pleiotropic cytokine and acts as a growth factor for murine plasmacytoma and human myeloma. IL-6 activates multiple signal transduction pathways. Among them, signal transducer and activator of transcription3 (STAT3), and the SHP-2-mediated Erk/MAP kinase pathway are important. The roles for the two major pathways in the IL-6-induced growth of B cell hybridoma cells were examined. A mutational analysis of the cytoplasmic domain of exogenously expressed gp130, a signal transducing beta chain of the IL-6 receptor complex, revealed that the proximal 133 amino acid (AA) region of gp130 with the intact Y767 but not Y759 is necessary and sufficient for gp130-signal-induced cell proliferation. Interestingly, no requirement of the Y759-mediated signals, including SHP-2-mediated Erk/MAP kinase pathway, coincided with the failure of SHP-2, Gab1/Gab2, and Erk/MAP kinase activation by IL-6 in MH60 cells. Moreover, we show that another serine/threonine kinase pathway leading to STAT3 Ser727 phosphorylation, which seemed to be derived from the Y767 in the proximal 133 AA residues, is intact in MH60 cells. Since Erk/MAP kinases are known to inhibit the subsequent IL-6-induced STAT3 activation, the impaired activation of Erk/MAP kinases by IL-6 may contribute to the development of B cell neoplasia.

B-Lymphocytes↗
PubMedDate not supplied

[Is physical training useful for elderly patients with ischemic heart disease?].

UNLABELLED: The aim of the paper is the study of the effects of a supervised physical training at old patients with ischaemic heart disease. METHODS: 74 patients with ischaemic left ventricular dysfunction have been followed during a supervised physical training consisting of a daily programme of exercise over a period of 21 +/- 10 days. They were parted in Group A (n = 26) over 60 years old and Group B (n = 48) under this age. The heart rate (HR), systolic and diastolic heart pressure (SHP respectively DHP), the time-tension index (TTI) were registered during the rest, the peak intensity of exercise and the recovery. These parameters were compared in evolution at each group and also between the groups. RESULTS: At Group A, at the end of the period, SHP at the peak intensity decreased (from 146 +/- 19 to 137 +/- 14 mmHg, p = 0.01), also SHP in the recovery period (from 119 +/- 10 to 116 +/- 10 mmHg, p = 0.01) and HR during the recovery time (from 77 +/- 8/min to 73 +/- 6/min, p = 0.03). The total length of the session time increased (from 12 +/- 4 min to 21 +/- 6 min, p = 0.01) and also the duration of the peak exercise time (from 3.6 +/- 1.0 min to 7.7 +/- 2.9 min, p = 0.03), in the condition of maintaining a HR at the peak exercise of about 75-76% of the maximum HR obtained at a previous exercise testing. The improvement of the training parameters was similar with Group B, except the duration of the session, longer at the last group (21 +/- 6 min at Group A vs. 25 +/- 7 min at Group B, p = 0.02) and the duration of the peak intensity (7.7 +/- 1.0 min at Group A vs. 9.1 +/- 2.9 min at Group B, p = 0.02). CONCLUSIONS: Old patients with ischaemic left ventricular dysfunction improve their exercise capacity as well as the younger ones; the benefits of a supervised physical exercise are evident regardless of age.

Adult↗
PubMed2004

Predicting the effect of intravenous calcitriol on parathyroid gland activity using double-phase technetium Tc 99m-sestamibi scintigraphy.

BACKGROUND: Although intravenous calcitriol is useful for decreasing intact parathyroid hormone (iPTH) blood levels in patients with secondary hyperparathyroidism (SHP) undergoing hemodialysis, approximately half these patients remain refractory to this treatment. The current study measures the diagnostic utility of double-phase technetium Tc 99m-sestamibi (MIBI) scintigraphy in predicting the response to calcitriol treatment. METHODS: Sixty hemodialysis patients with SHP with iPTH blood levels between 240 and 600 pg/mL (ng/L) were selected. Initial intravenous calcitriol pulse therapy was 6 microg/wk (for iPTH levels of 400 to 600 pg/mL [ng/L]) or 3 microg/wk (for iPTH levels of 240 to 400 pg/mL [ng/L]). MIBI scintigraphy was performed before the onset of calcitriol therapy and repeated 1 year later. Patients were injected intravenously with 740 MBq of MIBI. Images were obtained at 15 minutes (thyroid phase) and 2 hours (parathyroid phase) after radiotracer administration. Focal areas of increased MIBI uptake were considered pathological parathyroid glands. RESULTS: Forty-eight patients completed the study. After 1 year, iPTH levels had decreased significantly in 95.2% (47 patients), whereas good control (iPTH < 240 pg/mL [ng/L]) was reached in 70.8% (34 patients) and only 4 patients had iPTH levels greater than 400 pg/mL (ng/L; all were patients with 3 MIBI-positive areas at baseline determination). At baseline, there were 30 patients (62.5%) with MIBI positive areas (1, 2, or 3 areas), which decreased to 14 patients (29%) at the end of the study period. No patient showed 4 positive areas at any time. The 18 patients (37.5%) with no MIBI-positive area at baseline remained unchanged. CONCLUSION: MIBI scintigraphy is a reliable exploratory tool in predicting the response to treatment with intravenous calcitriol in hemodialysis patients with SHP.

Adult↗
PubMed2004

Biological activity of the virulence factor cagA of Helicobacter pylori.

BACKGROUND: China is one of the countries with the highest incidence of H. pylori and more than 9090 isolates possessed the cagA gene. This study was to evaluate the biological activity of the H. pylori virulence factor cagA isolated from Chinese patients. METHODS: cagA DNA fragments were amplified from the genomic DNA and subsequently cloned into the mammalian expression vector for cell transfection and DNA sequencing. cagA protein, phosphorylated-tyrosine cagA and the complex of cagA precipitated with SHP-2 were identified respectively by western blot in the crude cell lysate from conditionally immortalized gastric epithelial cells at 48 hours after transfection with cagA DNA. In addition, the ability of induction of scattering phenotype was examined after transient expression of cagA in AGS cells. RESULTS: The C-terminal half of cagA contained only one repeated sequence and three tandem five-amino-acid motifs glutamic acid-proline-isoleucine-tyrosine-alanine (EPIYA). Moreover, the amino acid sequence of D2 region in repeated sequence was aspartic acid-phenylanaline-aspartic acid (D-F-D) which was significantly distinguished from the three repeated sequences and aspartic acid-aspartic adid-leucine (D-D-L) in the western standard strain NCTC11637. Western blot revealed that cagA became phosphorylated in tyrosine site and bound with SHP-2 after transient expression of cagA DNA in gastric epithelial cells. Transient expression of cagA in AGS cells showed that cagA was able to induce the elongation phenotype although to a lesser extent than western strains. CONCLUSIONS: cagA perturbs cell signaling pathways by binding with SHP-2. However, significant difference exists in amino acid sequence and biological function of cagA in Chinese compared with those of western countries.

Amino Acid Sequence↗
PubMed2005

[Anti-hypertensive effects of PPARgamma ligands through the inhibition of Rho/Rho kinase pathway].

Although PPARgamma ligands have an antihypertensive effect in vivo, the precise mechanism has not been fully elucidated. We examined their effects on Rho/Rho kinase pathway, a key regulator of vascular tone. In cultured rat aortic smooth muscle cells, Rho kinase activated by angiotensin II was suppressed by the pretreatment with pioglitazone and troglitazone. The roles of Vav, a GTP/GDP exchange factor upregulating Rho kinase activity, and SHP-2, protein tyrosine phosphatase that dephosphorylated Vav and subsequently inactivated Rho kinase were examined. Both pioglitazone and troglitazone upregulated SHP-2, particularly in the cytosolic fraction, and the SHP-2-bound Vav, and reduced the phosphorylation of Vav. These mechanisms may contribute to the hemodynamic, in addition to metabolic, action by PPARgamma ligands in hypertensive, metabolic syndrome.

Acute-Phase Proteins↗
PubMed2005

[New therapy strategies in secondary hyperparathyroidism on dialysis (I): new concepts, new treatments].

Secondary hyperparathyroidism (SHP) is still an early and frequent complication of chronic renal disease (CRD). Currently, CRD is an independent cardiovascular risk factor, and calcium-phosphorus metabolism is one of the modifiable related factors. In this first article, we summarize the recent SHP treatment paradigm shift in dialysis patients, derived from the better knowledge and understanding of vascular calcification. We analyze the most recent guidelines (K/DOQI), and describe the general implications of hyperphosphatemia, as well as our therapeutic approach with phosphorus-binders. Since sevelamer additionally presents some pleiotropic effects and it attenuates the progression of vascular calcification, we consider it in the first-line of treatment despite it is not yet demonstrated a survival benefit. We also minimize the use of elemental calcium to a maximum of 1000 to 1500 mg/day. Lanthanum carbonate may well be an important therapeutic agent in the near future, especially if security concerns related to metal accumulation are overcome. Ferric citrate, colestilan and nicotinamide may soon play a role. All these drugs, isolated or in combination, are important in the treatment of SHP since a great deal of its success and the avoidance of some dialysis-related complications depend on an efficient phosphorus control.

Algorithms↗
PubMed1991

Influence of method of model fitting and gender on estimated parameters for the relationship between starvation heat production and body size in the domestic fowl.

The relationship between starvation heat production (SHP) in kJ/d and body weight (W) in kg for domestic fowl was examined with compiled calorimetric data for 294 fowls (Johnson and Farrell, 1985). Linear regression analyses using ordinary least squares methods were performed before and after transformation of the data to a logarithmic scale (base = 10). Coefficients of determination (R2) were similar for untransformed and log-transformed data (R2's = .56 and .53, respectively). The slopes for untransformed data of males and females were different (P less than 0.033). When the model parameters for: SHP = b0 Wb1 were derived from log-transformed data, there were no significant differences in exponents for males vs. females (P greater than .95). However, when the coefficients were estimated using non-linear regression techniques, a difference was detected at the level of P = 0.072. It was determined that there is no advantage in describing the relationship of SHP as a non-linear function of W, nor is it appropriate to express physiological variables as a ratio of weight raised to some mass exponent without statistical justification. Using W or W2 as a covariable for the statistical analysis of physiological data would produce equally acceptable determinations of significance.

Animals↗
PubMed1978

A new in vitro cell line established from human large cell variant of oat cell lung cancer.

A new tissue culture cell line, SHP-77, has been established from explant cultures of a primary human lung cancer. Although the latter exhibited histological features of the so-called large or polygonal cell undifferentiated variant, neurosecretory granules were detected ultrastructurally in cells of the original tumor, culture line, and neoplasms developing after transplantation of the latter in nude mice. These features attest to the identity of the original tumor as a large-cell variant of oat cell cancer. In addition, electron microscopy revealed the presence of gland formation and intracytoplasmic lamellar bodies in the cells of SHP-77. This information indicates the potential for varied differentiation and morphological expression of so-called undifferentiated lung cancer cells and is pertinent to nosological considerations concerning human lung cancer. The cell line has maintained its morphological, karyotypic, chromosomal, and growth characteristics after transplantation to nude mice. Because of this stability, SHP-77 appears to represent a propitious cell line for in vitro and in vivo biological and therapeutic studies of this type of lung cancer.

Animals↗
PubMed1990

Biased selection under the senior health plan prior use capitation formula.

A widely acknowledged shortcoming of the current AAPCC capitation formula for Medicare HMOs is its inability to adjust capitation levels for differences in health status among enrolled groups. Prior use models have been proposed as one alternative to the current AAPCC risk classes. From 1984 through 1987, Senior Health Plan (SHP) participated in a HCFA-sponsored demonstration project in which capitation payments were determined by a prior use formula incorporating information on inpatient hospital days and Part B deductibles. This paper contains findings about selection bias in SHP enrollment from analyses of preenrollment reimbursements and postenrollment mortality rates of SHP enrollees compared with Medicare FFS beneficiaries and enrollees of other Medicare HMOs in the Minneapolis-St. Paul area.

Capitation Fee↗
PubMed1983

[Calcium-phosphorus changes in chronic anticonvulsant therapy: effects of the administration of 25-hydroxyvitamin D3 on secondary hyperparathyroidism].

The present study represents a contribution to the knowledge of secondary hyperparathyroidism (SHP) in patients treated with anticonvulsant drugs (AC). In these subjects alterations of the calcium: phosphorus metabolism as rickets and osteomalacia are frequent; however literature data on SHP are scarce. Our research carried out on 29 adult patients under treatment with one or more AC for periods ranging from 9 months to 12 years confirmed that 25-OHD levels in the serum are low, especially in patients treated for longer times. The iPTH levels in the serum are increased with respect to normal controls, while blood calcium and phosphate levels are normal as are urine calcium and phosphate. The 25-OHD levels in serum present the same seasonal variations as the normal controls. The administration of 25-OHD3 (20 micrograms/day for 3 months) to 12 of these patients who had the lowest 25-OHD spring levels rendered the 25-OHD levels attain normal values. Cyclic AMP was normalized; serum and urine calcium and phosphorus and urinary hydroxyproline were not modified significantly. On the basis of the present data it is recommended that chronic AC treatment should be accompanied by long term administration of 25-OHD3 for prophylaxis and/or for treatment of SHP.

Adolescent↗
PubMed1983

[Immunogenetics of intercapillary glomerulonephritis due to IgA deposits].

Idiopathic mesangial IgA nephritis (Berger's disease) and Schönlein-Henoch purpura mesangial IgA nephritis (SHP) have a common immunopathological pattern. There is a weak association with the MHC class I antigen, B35, which is a poor prognosis marker in Berger's disease and which predisposes to renal involvement in SHP. There is also an association with the MHC class II antigen, DR4, whose signification remains unclear. Many familial cases of Berger's disease have been reported in patients bearing the HLA-B35 antigen. We proposed that Berger's disease and SHP should be viewed as a unique entity according to their common immunogenetics and also common immunopathology.

Capillaries↗
PubMed1994

[Hypersensitivity pneumonitis--histopathology of summer-type hypersensitivity pneumonitis].

Summer-type hypersensitivity pneumonitis(SHP) first reported by T. OCHI, et al. (1978), as a new type hypersensitivity pneumonitis(HP) with features of initiation during summer and anti-Cryptococcus antibody positive sera, has been recognized as "a unique disease in Japan", a most common type of HP in Japan, and now also known as anti-Trichosporon cutaneum antibody-positive SHP. This report was mainly concerned with the histopathology of SHP, thus far diagnosed in our hospital. Of the cases in our hospital, 62 consecutive biopsied cases (3 cases of open lung biopsy and 59 cases of transbronchial lung biopsy) without steroid institution before lung biopsy have been reviewed and revealed granulomatous interstitial pneumonitis in the bronchiolo-alveolar region, like various types of HP. Alveolitis (61 of 62 cases; 98.4%), sarcoid-like granuloma (50 of 62; 80.6%) and Masson's body (36 of 62; 58.1%) are main features, and could be named "triad" features. Concerning histopathological findings related with the period of lung biopsy after onset of clinical episodes as HP, alveolitis has been present regardless of period, and fibrinous exudate present in the early period and not in a case at 4 months. Sarcoid-like granuloma and Masson's body have appeared firstly at one-month cases. After this period sarcoid-like granuloma have been present in nearly all cases, but Masson's body has been not present in 10-month case with gradual decrease after 2 months, when all 2-month cases had it. In summary, for histopathological diagnosis of HP, the "triad" features and the time of lung biopsy done are keys, taking into consideration histopathological differential diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Alveolitis, Extrinsic Allergic↗
PubMed1995

[Experimental research on using macromolecule sodium hyaluronate to prevent flexior tendon adhesion].

With chicken paw as an animal model, we studied the effects of sodium hyaluronate product (SHP) on the heal of injured tendon and the formation of post-surgical tendon adhesions. The function of digit flexion angle and moving function of the tendon in SHP group were remarkably superior to those of tendons in physiological salt solution control group (P < 0.01). Tendons of the experiment group healed well, their surface was smooth without adhesion. False sheath was formed around the tendon, and there was also a gap between the false sheath and the tendon. However, the adhesion between the tendon and its surrounding tissue in the control group was donse with clear boundary. These results suggest that SHP has a protective effect against the formation of adhesion in healing tendon.

Animals↗