Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Factor For Inversion Stimulation Protein”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 541 records · Page 30Linked to original sources
PubMed2000

Interferons and IRF-1 induce expression of the survival motor neuron (SMN) genes.

BACKGROUND: Spinal muscular atrophy (SMA) is a common recessive disorder, characterized by degeneration of motor neurons of the spinal cord. Deletions, conversions, or mutations of the survival motor neuron gene (SMN) are responsible for SMA. A highly homologous centromeric copy of the SMN gene (SMNc) remains intact in SMA patients. However, there is an inverse correlation between the amount of the SMNc gene product and the clinical severity of the disease. An understanding of SMN and SMNc gene regulation is, therefore, an important step towards therapy for SMA. RESULTS: We identified a candidate Interferon-Stimulated Response Element (ISRE), overlapping with an Interferon Regulatory Factors binding motif (IRF-E) in the promoter region of SMN and SMNc genes. Both ISRE and IRF-E motifs are involved in mediating transcriptional induction of interferon-stimulated gene expression. We, therefore, investigated whether SMN and SMNc genes were regulated by interferons (IFN). Here we show that both IFN-beta and IFN-gamma rapidly induced SMN and SMNc mRNA and protein expression in various cell lines. The transcription factor IRF-1 bound to the candidate ISRE/IRF-E sequence of SMN and SMNc genes in vitro and overexpression of IRF-1 induced expression of both genes in transfection assays. IRF-1 is, therefore, at least in part responsible for the induction of SMN and SMNc by IFNs. In primary culture of fibroblasts from SMA patients, IFN-beta and IFN-gamma induced SMNc gene expression and restored protein defect.

Base Sequence↗
PubMed1996

Insulin-like growth factor binding protein-3 generation: an index of growth hormone insensitivity.

GH insensitivity may be an inherited condition or may arise as a consequence of disease of malnutrition. Laron syndrome is the most severe form of GH insensitivity, arising from an absent or defective GH receptor. Less severe forms of GH insensitivity, however, may exist, resulting in short stature but in few other features of Laron syndrome. We have identified a heterogeneous group of children with short stature and either high basal (> 10 mU/L) or high peak GH levels (> 40 mU/L) on GH provocation testing, to examine biochemical markers of GH sensitivity. These children received 4 d of GH (0.1 U/kg) and the increment in IGF-I, IGF binding protein (BP)-3, and GHBP was determined. Eight GHD children, commencing GH therapy, were recruited as positive controls. The two groups could not be differentiated by age, height SDS (SD score), height velocity SDS, or body mass index. IGF-I and IGFBP-3 generation were correlated in all children (delta SDS IGF-I versus delta SDS IGFBP-3, r = 0.49, p = 0.03). Neither basal GHBP levels or the increment in GHBP were predictive of the IGF-I or IGFBP-3 response to GH. The GHI group had a significantly reduced IGFBP-3 response to stimulation with 4 d of GH (median percent increment in IGFBP-3, 26%, versus 72% in the GHD group, P = 0.03); their IGF-I response to GH was also reduced (median % increment in IGF-I 75% versus 144% in the GH deficient group), but this did not achieve significance, p = 0.06. In all children, the percentage rise or delta SDS in both IGF-I and IGFBP-3 inversely correlated with the GH peak obtained on provocation testing, the latter being the most significant determinant of GH peak. We propose that the "IGF generation test", in particular IGFBP-3 generation, can be used in the investigation of partial GH insensitivity. Further work, however, is required to establish diagnostic criteria for partial GH insensitivity.

Adolescent↗
PubMed1999

Up-regulation by human recombinant transforming growth factor beta-1 of collagen production in cultured dermal fibroblasts is mediated by the inhibition of nitric oxide signaling.

BACKGROUND: Hypertrophic scarring remains the most disabling sequela for burn survivors. Little is known about its pathogenesis. Collagen accumulation, however, has been consistently observed in burn hypertrophic scars (HS). STUDY DESIGN: We have studied collagen production in the dermal fibroblasts derived from HS, which has developed for 9 months to 2 years. Reconstructive surgery was performed to remove HS from which the fibroblasts were cultured. Similarly, the normal cells were grown from the patient's donor site (DS), which provided autografting to the HS site. Collagen production in HS and DS fibroblasts was compared and analyzed in minimal essential amino acid medium containing 5% fetal bovine serum with inclusion of L-ascorbic acid (100 microg/mL) and beta-aminopropoinitrile (100 microg/mL) by monitoring a 20-h [3H]proline incorporation into bacterial collagenase III-digestible protein in the conditioned media. RESULTS: We failed to detect any significant difference in collagen production in vitro between HS and DS. Irrespective of the fibroblasts from HS or DS, collagen production was substantially stimulated by human recombinant transforming growth factor beta-1 (TGF-beta1) (20 ng/mL) by approximately 250% after a 3-day pretreatment. In contrast, sodium nitroprusside (SNP) at 100 microM exhibited significant suppression (68%), which was rescued by hemoglobin (10 microM). TGF-beta1 significantly decreased nitric oxide (NO) production by 55%. In contrast, NO level drastically increased by 350% following SNP treatment. Epidermal growth factor showed no effect on either collagen production or NO level. The linear regression analysis shows a significant inverse correlation (r = 0.72; p < 0.05) of NO level with collagen production, suggesting the involvement of NO signaling in the modulation of collagen production. Consistent with the notion, we further showed that N-nitro-L-arginine methyl ester (100 microM) caused a synergistic stimulation and an arrested inhibition of collagen production in the presence of TGFbeta-1 and SNP, respectively. 8-BrcGMP (300 microM) mimicked the NO inhibitory action, while methylene blue (50 microM) restored the collagen production which was inhibited by SNP. Moreover, 8-BrcGMP offset the stimulation of collagen production. CONCLUSIONS: The dermal fibroblasts derived from HS were not different from normals with respect to collagen production and their responses to regulations. The inhibition of collagen production was achieved by a cGMP-dependent NO action. TGFbeta-1 inhibited NO/cGMP signaling to ensure its stimulatory effect on collagen production in the dermal fibroblasts.

Burns↗
PubMed1991

Uterine binding sites for LH/hCG can be modulated by hormonal status in rabbits and rats.

High-affinity LH/hCG binding sites have been identified in both porcine and rabbit uteri. We have now identified these binding sites in rat uteri. We have assessed the binding site specificity and modulation and have searched for binding sites for a related glycoprotein. Radioreceptor assays were performed with membrane homogenates of uterine tissue, and were analysed for binding site specificity, affinity, and capacity. The rabbit and rat LH/hCG binding sites did not bind human TSH or human FSH. Rabbit uterine tissue contained no binding sites for FSH, as determined with 125I-labelled FSH and unlabelled FSH. Pretreatment of rabbits with hCG decreased their uterine binding site capacity from 1.30 +/- 0.29 to 0.46 +/- 0.01 fmol/mg protein. Pretreatment of castrated rabbits with estrogen or estrogen combined with progesterone did not alter the binding site affinity or capacity. In rats, the uterine binding site number was shown to vary inversely with the serum LH concentration and directly with the ovarian LH/hCG binding site number during the estrus cycle. Hypophysectomy resulted in a significant increase in uterine binding site capacity in rats. Estrogen treatment prevented this hypophysectomy-induced increase. The function of these LH/hCG binding sites remains uncertain; however, the lack of binding sites for a related glycoprotein and the modulation of these binding sites by hormonal factors strengthen the concept that uterine tissue might respond in a specific manner to direct LH/hCG stimulation.

Animals↗
PubMed1985

Caerulein and secretin induced pancreatic growth: a possible control by endogenous pancreatic somatostatin.

Pancreatic hypertrophy and hyperplasia following chronic joint (CA + SE), or separate, caerulein (CA: 1 microgram . kg-1) and secretin (SE: 75 micrograms . kg-1) administration were studied in parallel with pancreatic somatostatin (SRIF) contents following 2, 4, 7 and 10 days of treatment. Parameters indicative of pancreatic growth (tissue weight, DNA and protein contents, cellular protein concentrations) increased significantly after 2 days of CA or CA + SE and reached a plateau between days 4 and 10. SE merely induced a mild hypertrophy after 4 days. Endogenous pancreatic SRIF contents varied upon treatment, differently so with each peptide regimen. Indeed, CA and CA + SE treatments decreased total SRIF contents after 2 days with no effect thereafter. SE also decreased the latter after 2 days while significant increases were observed after 7 and 10 days. The inverse relationship seemingly existing between SRIF contents and the amplitude of hormonally-induced pancreatic growth supports the hypothesis that endogenous pancreatic SRIF, operating as an 'antigrowth' factor, may participate in the exogenous CA, SE and CA + SE stimulated pancreatic growth phenomena.

Animals↗
PubMed2003

Vitamin D and dexamethasone inversely regulate parathyroid hormone-induced regulator of G protein signaling-2 expression in osteoblast-like cells.

The PTH/PTHrP receptor stimulates both adenylate cyclase- and phospholipase C-dependent signaling pathways via different G proteins. The biological actions of PTH on bone are modified by steroid hormones. PTH induces expression of regulator of G protein signaling (RGS)-2, a putative preferential inhibitor of G(q)-mediated phospholipase C activation. We investigated whether steroid hormones interfere with PTH signaling by modulating PTH-induced RGS-2 expression in osteoblast-like UMR 106-01 cells. PTH (1-34) rapidly and transiently induced expression of RGS-2 mRNA and protein via the cAMP/protein kinase A pathway within 30 min, with maximal protein abundance after 2 h. PTH-induced RGS-2 preferentially bound to Galpha(q), compared with Galpha(s) protein. 1,25-(OH)(2)D(3) pretreatment enhanced PTH-induced RGS-2 mRNA and protein accumulation, whereas dexamethasone preincubation had an attenuating effect. These effects were due to modulation of the RGS-2 gene transcription rate, which increased by 35% with 1,25-(OH)(2)D(3) and decreased by 63% with dexamethasone pretreatment. RGS-2 mRNA half-life was not affected by either steroid. The transcriptional effects of dexamethasone and 1,25-(OH)(2)D(3) were independent of PTH/PTHrP receptor activation and were not explained by effects on cAMP accumulation, cAMP response element-binding protein expression or phosphorylation, or the abundance of the osteoblast-specific transcription factor core-binding factor alpha (CBFa1/Runx2), a known activator of RGS-2 expression. In conclusion, glucocorticoids and 1,25-(OH)(2)D(3) inversely modulate PTH-induced RGS-2 gene transcription. Regulation of RGS-2 may constitute a novel mechanism by which steroids modulate signaling via the PTH/PTHrP receptor and other G protein-coupled receptors in bone.

Animals↗
PubMed2003

The role of the novel adipocyte-derived hormone adiponectin in human disease.

Adiponectin, also called GBP-28, apM1, AdipoQ and Acrp30, is a novel adipose tIssue-specific protein that has structural homology to collagen VIII and X and complement factor C1q, and that circulates in human plasma at high levels. It is one of the physiologically active polypeptides secreted by adipose tIssue, whose multiple functions have started to be understood in the last few Years.A reduction in adiponectin expression is associated with insulin resistance in some animal models. Administration of adiponectin has been accompanied by a reduction in plasma glucose and an increase in insulin sensitivity. In addition, thiazolidinediones, drugs that enhance insulin sensitivity through stimulation of the peroxisome proliferator-activated receptor-gamma, increase plasma adiponectin and mRNA levels in mice. On the other hand, this adipocyte protein seems to play a protective role in experimental models of vascular injury. In humans, adiponectin levels are inversely related to the degree of adiposity and positively associated with insulin sensitivity both in healthy subjects and in diabetic patients. Plasma adiponectin levels have been reported to be decreased in some insulin-resistant states, such as obesity and type 2 diabetes mellitus, and also in patients with coronary artery disease. On the contrary, chronic renal failure, type 1 diabetes and anorexia nervosa are associated with increased plasma adiponectin levels. Concentrations of plasma adiponectin have been shown to correlate negatively with glucose, insulin, triglyceride levels and body mass index, and positively with high-density lipoprotein-cholesterol levels and insulin-stimulated glucose disposal. Weight loss and therapy with thiazolidinediones increased endogenous adiponectin production in humans. Adiponectin increases insulin sensitivity by increasing tIssue fat oxidation, resulting in reduced circulating fatty acid levels and reduced intracellular triglyceride contents in liver and muscle. This protein also suppresses the expression of adhesion molecules in vascular endothelial cells and cytokine production from macrophages, thus inhibiting the inflammatory processes that occur during the early phases of atherosclerosis. In view of these data, it is possible that hypoadiponectinemia may play a role in the development of atherosclerotic vascular disease. In summary, the ability of adiponectin to increase insulin sensitivity in conjunction with its anti-inflammatory and anti-atherogenic properties have made this novel adipocytokine a promising therapeutic tool for the future, with potential applications in states associated with low plasma adiponectin levels.

Adipocytes↗
PubMed1998

Thrombopoietin serum concentration in patients with reactive and myeloproliferative thrombocytosis.

We wished to test whether thrombopoietin (TPO) is entirely regulated by receptor binding or if other factors may play a role in the mechanism of TPO regulation. Therefore, we analyzed the TPO serum levels in 43 patients with reactive (secondary) thrombocytosis and in 37 with myeloproliferative thrombocytosis. Thrombocytosis was defined as a platelet level greater than 440 x 10(9)/l. Forty-two patients (98%) with reactive thrombocytosis had high concentrations of IL-6 correlating with elevated C-reactive protein levels. Twenty-three patients (53%) in this group had TPO serum concentrations of more than 300 pg/ml (normal: below 300 pg/ml). Only nine patients (24%) with myeloproliferative thrombocytosis had TPO serum levels above normal range, whereas 28 patients (76%) had normal levels of TPO. No correlation between the TPO serum levels and the concentrations of IL-6 or EPO was established. The other investigated thrombopoietic cytokines (IL-3, IL-11, GM-CSF) were unmeasurable; therefore, a correlation could not be assessed. We conclude that TPO concentrations are not strictly inversely related to platelet count. TPO serum levels are elevated especially in a considerable percentage of patients with reactive thrombocytosis, arguing for the existence of additional mechanisms of TPO regulation.

Adolescent↗
PubMed1992

3'-UTR-dependent deadenylation by the yeast poly(A) nuclease.

Poly(A) tail removal is the first step in the degradation pathway for some mRNAs. The purified poly(A)-binding protein (PAB)-dependent poly(A) nuclease (PAN) from yeast removes mRNA poly(A) tails in vitro by a process similar to that observed in vivo. The exonucleolytic PAN degrades poly(A) and RNA bound by PAB, and can be activated by spermidine to degrade poly(A) in the absence of PAB. The shortening of the poly(A) tail down to 10-25 nucleotides and the terminal deadenylation of this short adenine tract are kinetically distinct reactions. Poly(A) shortening rates are stimulated by the yeast a-mating factor (MFA2) RNA 3' UTR sequence, and this occurs by switching PAN from a distributive to a more processive enzyme. Terminal deadenylation rates are also stimulated to different extents by various RNAs. Inversion of the MFA2 3' UTR sequence completely inhibits the terminal deadenylation reaction owing to the presence of an inhibitory element 70 nucleotides from the poly(A) tail. Other sequence elements inserted at a similar distance from the poly(A) tail also interfere with the reaction. These data suggest that the two phases of poly(A) degradation can be regulated by mRNA sequences, and they provide a mechanistic description of how this regulation could occur in vivo.

Base Sequence↗
PubMed2005

Regulation of Fas-mediated apoptosis in neutrophils after surgery-induced acute inflammation.

BACKGROUND: Neutrophils undergo rapid Fas-mediated apoptosis during in vitro culture. The purpose of this study was to investigate the effects of surgical stress upon the Fas-mediated apoptotic response in circulating neutrophils. MATERIALS AND METHODS: Blood samples were drawn from eight patients with a mandibular prognathism, and who had undergone a bilateral sagittal split ramus osteotomy, at 2 days before, and at 1 and 5 days after surgery. The circulating neutrophils in each blood sample were then evaluated for their susceptibility to Fas-mediated apoptosis in either the presence or the absence of autogenous plasma. RESULTS: Fas-induced apoptosis in the neutrophils of these surgically treated patients was found to be slightly accelerated at 1 day postoperatively in the presence of FBS, compared with 2 days preoperatively and 5 days postoperatively. However, we obtained different results for these experiments in the presence of autogenous plasma. The Fas-induced apoptotic response levels in the neutrophils at day 1 postsurgery following exposure to autogenous plasma were significantly suppressed compared with the levels at both 2 days preoperatively and 5 days postoperatively. The Fas expression levels on the cell surface of the neutrophils were not altered, but the levels of soluble Fas (sFas) in the plasma were reduced to almost inverse levels during the postoperative periods. The levels of granulocyte-macrophage colony-stimulating factor, interleukin-6, and interleukin-8 levels in the plasma were also markedly raised in the plasma from each of these patients at 1 day postoperatively. However, the anti-apoptotic effects of the plasma on the Fas-mediated neutrophil apoptosis were not influenced by the addition of their neutralizing antibodies for these cytokines. The suppressive effects of postoperative plasma on Fas-mediated neutrophil apoptosis were blocked by the phosphatidylinositol 3-kinase (PI 3-K) inhibitors, LY294002, and wortmannin. Additionally, these effects were also abrogated by the extracellular signal-regulated kinase (ERK) inhibitor, PD98059, but not by the p38 mitogen-activated protein kinase inhibitor, SB203580. CONCLUSIONS: The increase in sFas levels in the plasma of patients with acute inflammation may lead to the inhibition of Fas-mediated neutrophil apoptosis. Moreover, the activation of the PI 3-K and ERK signaling-dependent pathways may, in part, also contribute to the down-regulation of the Fas-mediated apoptotic response in neutrophils.

Acute Disease↗
PubMed2002

Membrane topology inversion of SecG detected by labeling with a membrane-impermeable sulfhydryl reagent that causes a close association of SecG with SecA.

SecG stimulates protein translocation in Escherichia coli by facilitating the membrane insertion-deinsertion cycle of SecA. SecG was previously shown to undergo membrane topology inversion, since SecA-dependent protein translocation renders the membrane-protected region of SecG sensitive to external proteases. To examine this topology inversion in more detail without protease-treatment, SecG derivatives with a single cysteine residue at various positions were labeled in the presence and absence of protein translocation with a membrane impermeable SH reagent, 4-acetamido-4'-maleimidylstilbene-2-2'-disulfonic acid (AMS). Treatment of spheroplasts with AMS revealed that a cysteine residue in the cytoplasmic region of SecG could be labeled from the periplasm side only in the presence of protein translocation, whereas a cytoplasmic protein, elongation factor, Tu, remained unlabeled. Treatment of inverted membrane vesicles with AMS also revealed that cysteine residues in the periplasmic region were labeled from the cytoplasmic side of membranes only when protein translocation was in progress. This labeling required ATP, SecA and a precursor protein, and became more efficient as the position of the cysteine residue became closer to the C-terminus. Crosslinking analyses revealed that the interaction between SecG and SecA in membranes markedly increases when SecA and SecG undergo membrane-insertion and topology inversion, respectively. Thus, the two most dynamic components of the translocation machinery were found for the first time to interact with each other when both undergo conformational changes.

Adenosine Triphosphatases↗
PubMed2005

Imaging epidermal growth factor receptor phosphorylation in human colorectal cancer cells and human tissues.

In tumor cells, high phosphorylation levels of receptor tyrosine kinases may occur in the absence of exogenous ligands due to autocrine signaling or enhanced tyrosine kinase activity. Here we show that the phosphorylation state of the endogenous epidermal growth factor receptor (EGFR) can be quantitatively imaged in tumor cells and tissues by detecting fluorescence resonance energy transfer between fluorophores conjugated to antibodies against the receptor and phosphotyrosine, respectively. Five different human colorectal cell lines were analyzed for activity and expression of EGFR. All cell lines exhibited basal EGFR phosphorylation under serum starvation conditions. Phosphorylation levels increased after stimulation with EGF or pervanadate, dependent on the level of basal EGFR phosphorylation in the respective cell lines. This basal activity correlated inversely with receptor expression. Using the acceptor photobleaching fluorescence resonance energy transfer imaging approach, a significantly higher phosphorylation state of EGFR was also found in resected human colorectal tumor samples as compared with adjacent healthy tissue. Imaging of EGFR phosphorylation may thus serve as a valuable tool to investigate the role of receptor tyrosine kinase activity in malignant cell growth.

Cell Line, Tumor↗
PubMed1989

Angiotensin II stimulates early proximal bicarbonate absorption in the rat by decreasing cyclic adenosine monophosphate.

These studies explored the hypothesis that angiotensin II increases bicarbonate absorption in the proximal convoluted tubule (PCT) by decreasing intracellular cAMP. In vivo microperfusion was performed in rat PCT with measurements of bicarbonate absorption and of tubular fluid cAMP delivery, as a reflection of intracellular cAMP. Intravenous angiotensin II potently increased S1 PCT bicarbonate absorption (348 +/- 11 to 588 +/- 8 peq/min.min, P less than 0.001) and decreased tubular fluid cAMP (18 +/- 2 to 12 +/- 2 fmol/mm.min, P less than 0.05). Parathyroid hormone had the expected opposite effects, which were additive to those of angiotensin II. Over a wide range of hormonal activities, there was an excellent inverse relationship between hormonally modulated bicarbonate absorption and cAMP delivery. Pertussis toxin pretreatment significantly attenuated (by 35-45%) the angiotensin-induced increase in bicarbonate absorption and decrease in cAMP delivery, indicating Gi-protein intermediation. Luminal dibutyryl cAMP abolished the transport response to angiotensin II. In conclusion, these in vivo results suggest angiotensin II stimulates bicarbonate absorption in the S1 PCT by a G1-mediated depression in intracellular cAMP.

Adenylyl Cyclases↗
PubMed2006

Genome multiplication as adaptation to tissue survival: evidence from gene expression in mammalian heart and liver.

To elucidate the functional significance of genome multiplication in somatic tissues, we performed a large-scale analysis of ploidy-associated changes in expression of non-tissue-specific (i.e., broadly expressed) genes in the heart and liver of human and mouse (6585 homologous genes were analyzed). These species have inverse patterns of polyploidization in cardiomyocytes and hepatocytes. The between-species comparison of two pairs of homologous tissues with crisscross contrast in ploidy levels allows the removal of the effects of species and tissue specificity on the profile of gene activity. The different tests performed from the standpoint of modular biology revealed a consistent picture of ploidy-associated alteration in a wide range of functional gene groups. The major effects consisted of hypoxia-inducible factor-triggered changes in main cellular processes and signaling pathways, activation of defense against DNA lesions, acceleration of protein turnover and transcription, and the impairment of apoptosis, the immune response, and cytoskeleton maintenance. We also found a severe decline in aerobic respiration and stimulation of sugar and fatty acid metabolism. These metabolic rearrangements create a special type of metabolism that can be considered intermediate between aerobic and anaerobic. The metabolic and physiological changes revealed (reflected in the alteration of gene expression) help explain the unique ability of polyploid tissues to combine proliferation and differentiation, which are separated in diploid tissues. We argue that genome multiplication promotes cell survival and tissue regeneration under stressful conditions.

Adaptation, Physiological↗
PubMed2004

Role of putrescine in regulation of the sigmaS subunit of RNA polymerase in Escherichia coli cells on transition to stationary phase.

Expression of the rpoS gene encoding the sigmaS subunit of E. coli RNA polymerase was studied on transition to the stationary phase and under conditions of starvation. Polyamines, in particular putrescine, are involved in regulation of the rpoS expression by concentration-dependent stimulation at the levels of translation and stability of the protein sigmaS. The stimulatory effect of exogenous putrescine inversely depended on its content in the cell and was the most pronounced in the beginning of the exponential growth. Possible mechanisms of the polyamine effect on the rpoS expression on post-transcriptional and post-translational levels are discussed.

DNA-Directed RNA Polymerases↗
PubMed1977

Effect of infection on food intake and the nutritional state: perspectives as viewed from the village.

Data from a prospective study of a Guatemalan village population revealed an exceedingly high force of infection which may effect nutrition and growth from gestation onward. Maternal morbidity was higher and fetal antigenic stimulation was more frequent than in industrial societies. Infection of the young child was a common occurrence and although a great many infections were silent, morbidity rates were extremely high, particularly during the protracted weaning period (6 to 24 months). Infectious disease was found to be an important cause of weight loss, arrest in height, and impaired physical growth. Also, it was a common precipitating factor of severe malnutrition and death. Analysis of the dietary data of fully weaned children did not reveal a deficit in protein intake. Most children, however, had very low calorie intakes. Infectious disease was a common cause of anorexia and of marked reduction in calorie intake, followed by weight loss and impaired physical growth. A strong inverse correlation was detected between infectious disease and calorie intake in the 2nd year of life, when children were being weaned. Infection is the most important isolated factor in the causation of malnutrition in the village. A reorientation of health and nutrition policies seems in line in view of failures of food supplementation programs, particularly with protein, in many parts of the world.

Breast Feeding↗
PubMed1994

Appearance of a megakaryocyte growth-promoting activity, megapoietin, during acute thrombocytopenia in the rabbit.

Plasma obtained from rabbits made thrombocytopenic by the injection of antiplatelet serum (APS) stimulated megakaryocyte growth in an in vitro bone marrow culture. Although the number of megakaryocytes that grew was increased on average to 136%, the major effect was on megakaryocyte ploidy, which showed a shift in the modal ploidy class from 8N to 16N, an average change in the geometric mean ploidy from 8.7N to 11.8N, and the appearance of some 64N megakaryocytes. This in vitro stimulation of megakaryocyte number and ploidy was shown to be due to the appearance in the circulation of a positive activity, which we have named megapoietin. Levels of megapoietin in thrombocytopenic plasma could be quantitated by measuring the extent of megakaryocyte ploidization in vitro. The relationship over time of megapoietin to changes in the platelet count was then assessed in a series of rabbits made thrombocytopenic by APS injection. Although not elevated after 3 hours of thrombocytopenia, megapoietin increased after 8 hours to 48% of the maximal level, which occurred after 24 hours of thrombocytopenia. Levels of megapoietin were inversely and proportionally related to the platelet count during thrombocytopenia and the subsequent rebound thrombocytosis. During persistent thrombocytopenia, megapoietin levels remained maximally elevated. These results suggest that megapoietin may play a physiologic role in the feedback loop between the platelet and the bone marrow megakaryocytes.

Animals↗
PubMed2002

Marked improvement of thrombocytopenia in a murine model of idiopathic thrombocytopenic purpura by pegylated recombinant human megakaryocyte growth and development factor.

OBJECTIVE: We examined the stimulatory effect of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) on platelet production in male (NZW x BXSB) F(l) (W/B F(1)) mice, a murine model of idiopathic thrombocytopenic purpura. MATERIALS AND METHODS: A cohort of 19- to 25-week-old, severely thrombocytopenic male W/B F(1) mice were given PEG-rHuMGDF at different dosing schedules. Before and at various times after therapy, platelet counts, reticulated platelets, platelet lifespan, and levels of platelet-associated immunoglobulin G were measured. Analysis of megakaryocytic cells was performed. RESULTS: Treatment of male W/B F(1) mice with PEG-rHuMGDF (30 microg/kg/day) three times per week for several weeks resulted in sustained thrombocytosis, accompanied by increased megakaryocytopoiesis in both the bone marrow and spleen. The degree of the platelet response to PEG-rHuMGDF varied between individual mice, likely reflecting the heterogeneity of the disease. Production of new platelets in response to PEG-rHuMGDF was manifested by an increase in reticulated platelets. Levels of platelet-associated immunoglobulin G decreased inversely during periods of thrombocytosis. PEG-rHuMGDF therapy also improved thrombocytopenia in male W/B F(1) mice refractory to splenectomy. Platelet lifespan was not affected by PEG-rHuMGDF. Male W/B F(1) mice treated with pegylated murine MGDF, a homologue of PEG-rHuMGDF, had persistent thrombocytosis for at least 7 months, suggesting that antiplatelet antibody production was not enhanced. CONCLUSIONS: PEG-rHuMGDF therapy potently stimulated platelet production, effectively ameliorating thrombocytopenia in a murine model of idiopathic thrombocytopenic purpura.

Animals↗