Cervical spine movements during laryngoscopy.
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Humans↗
Biomedical subjects
K Gupta
Publications and source records attributed to K Gupta.
Pituitary hyperplasia resulting from primary hypothyroidism mimicking macroadenomas.
Three patients presented with clinical and imaging features suggestive of a primary functional pituitary adenoma. Surprisingly, thyroid function testing revealed co-existing primary hypothyroidism. The pituitary tumours represented hyperplasia of anterior pituitary thyrotrophs secondary to hypothyroidism. Complete regression was achieved with thyroxine replacement therapy. Careful attention should be paid to differentiating this condition from prolactinoma or the rare TSH producing adenoma.
Adenoma↗
Epidermal growth factor receptor-mediated motility in fibroblasts.
Cell motility is induced by many growth factors acting through cognate receptors with intrinsic tyrosine kinase activity (RPTK). However, most of the links between receptor activation and the biophysical processes of cell motility remain undeciphered. We have focused on the mechanisms by which the EGF receptor (EGFR) actuates fibroblast cell motility in an attempt to define this integrated process in one system. Our working model is that divergent, but interconnected pathways lead to the biophysical processes necessary for cell motility: cytoskeleton reorganization, membrane extension, formation of new adhesions to substratum, cell contraction, and release of adhesions at the rear. We postulate that for any given growth factor some of the pathways/processes will be actively signaled and rate-limiting, while others will be permissive due to background low-level activation. Certain couplings have been defined, such as PLCgamma and actin modifying proteins being involved in cytoskeletal reorganization and lamellipod extension and MEK being implicated in detachment from substratum. Others are suggested by complementary investigations in integrin-mediated motility, including rac in membrane protrusion, rho in new adhesions, myosin II motors in contraction, and calpain in detachment, but have yet to be placed in growth factor-induced motility. Our model postulates that many biochemical pathways will be shared between chemokinetic and haptokinetic motility but that select pathways will be activated only during RPTK-enhanced motility.
Actins↗
Human CD34(+) bone marrow cells regulate stromal production of interleukin-6 and granulocyte colony-stimulating factor and increase the colony-stimulating activity of stroma.
Cytokines produced by stromal cells induce the proliferation and differentiation of hematopoietic cells in the marrow microenvironment. We hypothesized that cross-talk between hematopoietic cells at different stages of differentiation and stromal cells influences stromal cytokine production and is responsible for maintaining steady-state hematopoiesis and responding to stress situations. We show that coculture of primitive CD34(+) cells in contact with or separated by a transwell membrane from irradiated human bone marrow stromal layers induces a fourfold to fivefold increase in interleukin-6 (IL-6) and granulocyte colony-stimulating factor (G-CSF) levels in the stromal supernatant (SN) during the first week. Levels of both cytokines decreased to baseline after coculture of CD34(+) cells for 3 to 5 weeks. Coculture of more mature CD15(+)/CD14(-) myeloid precursors induced only a transient 1.5- to 2-fold increase in IL-6 and G-CSF at 48 hours. Neither CD34(+) nor CD15(+)/CD14(-) cells produced IL-6, G-CSF, IL-1beta, or tumor necrosis factor alpha. When CD34(+) cells were cultured in methylcellulose medium supplemented with cytokines at concentrations found in stromal SN or supplemented with stromal SN, a fourfold to fivefold increase in colony formation was seen over cultures supplemented with erythropoietin (EPO) only. When cultures were supplemented with the increased concentrations of IL-6 and G-CSF detected in cocultures of stroma and CD34(+) cells or when CD34(+) cells were cocultured in methylcellulose medium in a transwell above a stromal layer, a further increase in the number and size of colonies was seen. The colony-forming unit-granulocyte-macrophage-stimulating activity of stromal SN was neutralized by antibodies against G-CSF or IL-6. These studies indicate that primitive CD34(+) progenitors provide a soluble positive feedback signal to induce cytokine production by stromal cells and that the observed increase in cytokine levels is biologically relevant.
Antigens, CD34↗
The toxic shock syndrome and Staphylococcus lugdunensis bacteremia.
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Adult↗
Mmip1: a novel leucine zipper protein that reverses the suppressive effects of Mad family members on c-myc.
C-myc, a member of the basic helix-loop-helix-leucine zipper (bHLH-ZIP) protein family activates target genes in heterodimeric association with another bHLH-ZIP protein, Max. Max readily homodimerizes, competes with C-myc-Max heterodimers, and represses transcription. Four additional bHLH-ZIP proteins, Mad1, Mxi1, Mad3 and Mad4, heterodimerize with Max and also repress transcription of c-myc-responsive genes. We employed a yeast two-hybid approach to identify proteins which interact with Mxi. We identified a novel ZIP-containing protein, Mmip1 (Mad member-interacting protein 1) that strongly dimerizes with all four Mad members, but not with c-myc, Max, or with unrelated HLH proteins. The Mmip1-Mxi association is mediated by the ZIP domain of each polypeptide and is as strong or stronger than the associations between c-myc and Max or Max and Mxi1. In vitro, Mmip1 can inhibit DNA binding by Max-Mad heterodimers and, in vivo, can reverse the suppressive effects of Mad proteins on c-myc functions. Mmipl is found in a variety of cells types, is induced by serum stimulation, and can be co-immunoprecipitated from fibroblasts in association with Mxi1. By interfering with the dimerization between Max and Mad family member proteins, Mmip1 can indirectly up-regulate the transcriptional activity of c-myc and suppress the antiproliferative actions of Mad proteins.
Amino Acid Sequence↗
Thrombin-stimulated calcium mobilization is inhibited by thrombospondin via CD36.
Activation of the G-protein-linked thrombin receptor in endothelial cells normally leads to an increase in free intracellular calcium, [Ca2+]i, which is the proximate stimulus for many important cell functions. We present evidence showing that signals from CD36, the thrombospondin (TSP) receptor, can inhibit this thrombin-mediated calcium response. Human endothelial cells preloaded with Indo-1 exhibited rapid calcium mobilization in response to thrombin. The presence of TSP inhibited the thrombin-stimulated calcium response in CD36-positive microvascular endothelial cells but not in CD36-negative umbilical vein endothelial cells. This TSP effect was mimicked by anti-CD36 antibodies and a TSP peptide (CSVTCG), but not by an alternative CD36 ligand (collagen IV) or an antibody to an alternative TSP receptor (alphavbeta3). TSP also inhibited the calcium response to the thrombin receptor-tethered ligand peptide, SFLLRN. In addition, TSP and anti-CD36 antibodies inhibited the calcium response of a closely related receptor, the trypsin/SLIGKVD-activated receptor PAR-2. TSP did not indiscriminately inhibit all calcium release pathways, since histamine- or VEGF-stimulated calcium responses were not inhibited by TSP. We conclude that cross-talk from the CD36 receptor influences the responsive state of the endothelial thrombin receptor family and/or its signaling pathway.
CD36 Antigens↗
Adjuvant bone marrow infusion in clinical organ transplant recipients.
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Bone Marrow Transplantation↗
Mechanism of biochemical action of substituted 4-methylbenzopyran-2-ones. Part II: Mechanism-based inhibition of rat liver microsome-mediated aflatoxin B1-DNA binding by the candidate antimutagen 7,8-diacetoxy-4-methylcoumarin.
7,8-Diacetoxy-4-methylcoumarin (DAMC), with no prerequisite for oxidative biotransformation has been reported to produce suicide inactivation of microsomal cytochrome P-450-catalysed formation of aflatoxin B1-8,9-oxide that binds to DNA. Parenteral administration of DAMC to rats caused significant inhibition of AFB1 binding to hepatic DNA in vivo as well as AFB1-induced micronuclei formation in bone marrow cells. These results highlight the antimutagenic potential of DAMC.
7-Alkoxycoumarin O-Dealkylase↗
Giant cell tumor of the sphenoid bone.
OBJECTIVE AND IMPORTANCE: Giant cell tumor of the sphenoid bone is extremely unusual. This tumor is usually located in long bones and is rarely located in the cranial vault. It must be differentiated from reparative granuloma and the Brown tumor of hyperparathyroidism. This case report is only the second involving a patient in the first decade. CLINICAL PRESENTATION: A 9-year-old girl presented with cephalgia and diplopia. Radiographic imaging revealed an erosive mass in the clivus. INTERVENTION: The patient underwent an extended transphenoidal resection of the clivus. This was followed with 57.6 CGE in 32 fractionated doses. CONCLUSION: At 1 year follow-up, the tumor remains stable. Based on anecdotal evidence, attempted resection with adjuvant radiation therapy allows for long-term survival in these patients.
Case Reports↗
Inverse association of H2O2-producing lactobacilli and vaginal Escherichia coli colonization in women with recurrent urinary tract infections.
Women with recurrent urinary tract infection (UTI) often demonstrate persistent vaginal colonization with Escherichia coli. Since strains of lactobacilli that produce hydrogen peroxide inhibit the growth of E. coli, the absence of these strains may predispose to E. coli colonization and to UTI. To test this hypothesis, vaginal introital cultures were obtained from 140 women, 65 with recurrent UTI (case-patients) and 75 without (controls). Vaginal E. coli colonization was significantly more frequent in case-patients than controls (35% vs. 11%; P < .001) and in women without H2O2-positive lactobacilli than in women with (odds ratio [OR], 4.0; P = .01). Spermicide use was associated with greater risk of vaginal E. coli colonization (OR, 12.5; P < .001) and with absence of H2O2-positive lactobacilli (OR, 2.9; P = .04). The inverse association between H2O2-positive lactobacilli and vaginal E. coli colonization remained in case-patients after controlling for spermicide use (OR, 6.5; P = .02). Thus, absence of H2O2-positive lactobacilli may be important in the pathogenesis of recurrent UTI by facilitating E. coli introital colonization.
Adult↗
EGF receptor regulation of cell motility: EGF induces disassembly of focal adhesions independently of the motility-associated PLCgamma signaling pathway.
A current model of growth factor-induced cell motility invokes integration of diverse biophysical processes required for cell motility, including dynamic formation and disruption of cell/substratum attachments along with extension of membrane protrusions. To define how these biophysical events are actuated by biochemical signaling pathways, we investigate here whether epidermal growth factor (EGF) induces disruption of focal adhesions in fibroblasts. We find that EGF treatment of NR6 fibroblasts presenting full-length WT EGF receptors (EGFR) reduces the fraction of cells presenting focal adhesions from approximately 60% to approximately 30% within 10 minutes. The dose dependency of focal adhesion disassembly mirrors that for EGF-enhanced cell motility, being noted at 0.1 nM EGF. EGFR kinase activity is required as cells expressing two kinase-defective EGFR constructs retain their focal adhesions in the presence of EGF. The short-term (30 minutes) disassembly of focal adhesions is reflected in decreased adhesiveness of EGF-treated cells to substratum. We further examine here known motility-associated pathways to determine whether these contribute to EGF-induced effects. We have previously demonstrated that phospholipase C(gamma) (PLCgamma) activation and mobilization of gelsolin from a plasma membrane-bound state are required for EGFR-mediated cell motility. In contrast, we find here that short-term focal adhesion disassembly is induced by a signaling-restricted truncated EGFR (c'973) which fails to activate PLCgamma or mobilize gelsolin. The PLC inhibitor U73122 has no effect on this process, nor is the actin severing capacity of gelsolin required as EGF treatment reduces focal adhesions in gelsolin-devoid fibroblasts, further supporting the contention that focal adhesion disassembly is signaled by a pathway distinct from that involving PLCgamma. Because both WT and c'973 EGFR activate the erk MAP kinase pathway, we additionally explore here this signaling pathway, not previously associated with growth factor-induced cell motility. Levels of the MEK inhibitor PD98059 that block EGF-induced mitogenesis and MAP kinase phosphorylation also abrogate EGF-induced focal adhesion disassembly and cell motility. In summary, we characterize for the first time the ability of EGFR kinase activity to directly stimulate focal adhesion disassembly and cell/substratum detachment, in relation to its ability to stimulate migration. Furthermore, we propose a model of EGF-induced motogenic cell responses in which the PLCgamma pathway stimulating cell motility is distinct from the MAP kinase-dependent signaling pathway leading to disassembly and reorganization of cell-substratum adhesion.
Animals↗
The profile of the cytokines secreted during the generation of T-helper cells from atopic asthmatic subjects.
This study investigated cytokine release by T-cell lines from atopic and nonatopic individuals in the presence of specific aeroallergen. Cell lines from atopic and nonatopic individuals secreted IL-2 for less than 14 and more than 21 days, respectively. All of the atopic, but not the nonatopic, cell lines exhibited a biphasic peak in IL-4 and IL-5 secretion. Flow cytometry revealed that, after 35 days, 89.3% of the atopic cells were T helpers and 73.2% were activated. Only 7.4% of the nonatopic cells displayed activation markers. In conclusion, T-cell differentiation may be controlled by other factors in addition to stimulation by aeroallergens.
Adult↗
Remineralizing efficacy of a mineral enriched mouth rinse and fluoridated dentifrice on artificial carious lesions: an in vivo scanning electron microscopic study.
This comparative investigation was carried out to evaluate the remineralization potential on early artificial carious lesions under Scanning Electron Microscope (SEM) of a Mineral enriched mouthrinse and a fluoridated dentifrice using an in-vivo intra-oral removable appliance model. This findings revealed that the remineralization was found to have occurred in almost all the samples (in children) using non-fluoridated, fluoridated dentifrices as well as those using mineral enriched mouthrinse. However the qualitative analysis of the remineralization revealed that in case of non-fluoridated dentifrice group, the prismatic holes showed deposition of granular, variable sized particles with uneven distribution, while in fluoridated dentifrice group, deposits were found to have partially but more densely filled up the prism cores. In case of mineral enriched mouthrinse group these deposits were found to be in the form of amorphous globular precipitate.
Adolescent↗
Aflatoxin B1-induced micronuclei and cell cycle alterations in lung and bone marrow cells and their modulation by Piper argyrophyllum extract.
Aflatoxin B, (AFB1) is a clastogen that causes cellular damage by covalent modification of nucleic acids. In this investigation, male rats were injected i.p. with AFB1 (8 mg/kg b.w.) in DMSO and the same dose of AFB1 was also administered intratracheally (i.t.) to the animals separately. The animals were killed after 26 h of the carcinogen treatment, femur bone was removed, and bone marrow cells were isolated and stained with Mayer's hematoxylin and eosin. Micronuclei (Mn) were scored by using light microscopy. Bronchoalveolar lavage (BAL) was prepared from rats administered AFB1 i.t. A part of BAL was fixed with 70% ethanol, stained with the fluorochrome DAPI, and analysed for cell cycle variations; the other part of the lavage was used for making slides to record Mn with a fluorescent microscope. A significantly greater proportion of lung cells were found to enter cell cycle with extended S-phase due to AFB1 treatment. Mn were induced in polychromatic erythrocytes (PCE) as compared to normochromatic erythrocytes (NCE) in the bone marrow of AFB1-treated rats, where there was nearly a three-fold increase in the number of Mn of bone marrow cells. The administration of AFB1 resulted in a two-fold rise in the Mn in the lung cells. The effect of BSO, DEM, and PB, the modulators of AFB1 metabolism, was studied on AFB1-induced Mn formation. A significant increase in the Mn score in PCEs of BSO- and DEM-treated rats was noted, while a slight reduction in the Mn score was noted in the case of PB-treated rats. The administration of the methanol extract of the leaves of Piper argyrophyllum (taken up in DMSO) to rats for a week exhibited normalising effect on AFB1-induced Mn in bone marrow cells. These observations record the induction of Mn in lung cells due to AFB1 for the first time. We propose the utility of AFB1-induced Mn as a model for screening plant extracts as inhibitors of genotoxicity. Prevention of genotoxic changes described above by phytochemicals is being pursued in our Laboratories.
Aflatoxin B1↗
The concentration-dependent membrane activity of cecropin A.
Cecropin A is a naturally occurring, linear, cationic, 37-residue antimicrobial peptide. The precise mechanism by which it kills bacteria is not known, but its site of action is believed to be the cell membrane. To investigate the nature of its membrane activity, we examined the ability of cecropin A to alter membrane permeability in synthetic lipid vesicles and in Gram-negative bacteria. Cecropin A exerted distinctly different types of membrane activity depending on its concentration. In synthetic lipid vesicles, cecropin A dissipated transmembrane electrochemical ion gradients at relatively low concentrations, but much higher concentrations were required to release an encapsulated fluorescent probe. Cecropin A dissipated ion gradients whether or not the vesicle membranes contained anionic lipid, although the presence of anionic lipid dramatically increased peptide binding, and modestly increased the release of an encapsulated probe. Cholesterol did not prevent the dissipation of ion gradients by low concentrations of peptide, but it did inhibit release of the encapsulated probe by high concentrations of peptide. At the highest concentrations examined, cecropin A remained monomeric in solution, and did not aggregate, lyse, or otherwise alter vesicle size. In Gram-negative bacteria, cecropin A was potently bactericidal at concentrations which dissipated ion gradients in lipid vesicles, but much higher concentrations were required to cause the release of cytoplasmic contents. These findings point to the conclusion that cecropin A kills bacteria by dissipating transmembrane electrochemical ion gradients. They weigh against theories comparing the antimicrobial activity of cecropin A to the release of encapsulated probes from lipid vesicles, and against roles for cholesterol or anionic lipid headgroups in the selectivity of peptide action against bacteria.
Amino Acid Sequence↗
A novel technique for culture of human dermal microvascular endothelial cells under either serum-free or serum-supplemented conditions: isolation by panning and stimulation with vascular endothelial growth factor.
Several physiological and pathophysiological events involving vascular endothelium occur at the microvascular level. Studies on human microvasculature require homogenous primary cultures of microvascular endothelial cells. However, procedures available for isolating and culturing human dermal microvascular cells (HDMEC) result in significant contamination with fibroblasts. To eliminate contamination with fibroblasts or other cells, we developed a procedure to isolate HDMEC from neonatal human foreskin by panning the cells using EN4, an anti-endothelial cell monoclonal antibody. Panned cells uniformly expressed von Willebrand factor and CD36, confirming their microvascular endothelial characteristics, whereas cells cultured without panning showed a significant degree of contamination with fibroblasts. In the presence of vascular endothelial growth factor (VEGF), HDMEC could be cultured under serum-free conditions. VEGF stimulated the growth of HDMEC in a dose-dependent manner in serum-free medium or in media supplemented with either human serum or newborn calf serum. Since differences exist between large vessel endothelial cells and microvascular endothelial cells, we compared the response to VEGF stimulation of HDMEC with human umbilical vein endothelial cells (HUVEC). The dose response of the two cell types to VEGF was different. This effect of VEGF on endothelial cells may be mediated by the VEGF receptor kdr, since mRNA for kdr was detected using RT-PCR in both HDMEC and HUVEC. The procedure described in this study will make possible the culture of highly enriched HDMEC without contamination with fibroblasts and facilitate studies with these cells under defined assay conditions in a serum-free environment.
Animals↗
Apparent poisoning by wood preservatives: an attributional syndrome.
Recent reports have pointed to an increased number of patients presenting with multisystem symptoms which they attribute to chemical exposures or to heightened chemical sensitivity. Twenty patients exposed to wood preservative products, who attended a joint toxicology and psychiatric clinic, were reviewed by a retrospective case note analysis. Thirteen patients attributed their symptoms to the wood preservative soon after the exposure, and seven patients developed the attribution only at a later date. Reported symptoms referred to all body systems, but there were few physical signs. Clinical findings suggest that the acute symptoms were consistent with the expected toxic effects, but the chronic symptoms could not be explained physically. Patient's beliefs about chemical poisoning could be understood as arising in the context of an attributional process, representing a sociopsychosomatic syndrome precipitated by wood preservative exposure. Patient management included a discussion of findings from assessments, published information, along with counseling where appropriate. Follow-up information from their general practitioners indicated a possible improvement in 50% of patients.
Adult↗