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Biomedical subjects

C Walker

Publications and source records attributed to C Walker.

At least 271 records · Page 15Linked to original sources

Molecular cloning of CD31, a putative intercellular adhesion molecule closely related to carcinoembryonic antigen.

cDNA clones encoding CD31 have been isolated by transient expression. The sequence of CD31 expressed on human umbilical vein endothelial cells (HUVEC) is identical to that expressed on the monocyte-like cell line HL60. In HUVEC. CD31 is concentrated in regions of cell-cell contacts. CD31 is a member of the Ig superfamily and is most closely related to the carcinoembryonic antigen CEA, consisting of four contiguous C2 domains. The localization of CD31 to regions of cell-cell contacts, and the sequence similarity to CEA, a known intercellular adhesion molecule (ICAM), strongly suggest that CD31 may function as an ICAM, possibly mediating endothelial cell-cell contacts and also promoting interactions between leukocytes and endothelial cells.

Amino Acid Sequence↗

Nonrandom chromosome alterations that correlate with progression to immortality in rat tracheal epithelial cells transformed with N-methyl-N'-nitro-N-nitrosoguanidine.

Primary rat tracheal epithelial cells can be transformed in vitro by N-methyl-N'-nitro-N-nitrosoguanidine. The earliest recognizable morphological transformant is the enhanced growth variant (EGV), characterized by enhanced proliferative capacity. Transformed EGV colonies can progress to give rise to immortal cell lines. The purpose of this study was to determine if specific chromosome changes occur which correlate with immortalization. A total of 34 EGV colonies were isolated, of which five were able to progress in culture to become immortal (greater than or equal to 100 population doublings). Early passages of all five immortalized cultures exhibited additional copies of chromosomes 4, 7, and 11 as a common or recurrent abnormality. These numerical alterations were rarely observed in the primary EGV colonies from which the cell lines were derived, suggesting that these alterations occurred during progression. Structural alterations involving chromosome 1 (resulting in a net gain of 1q) and chromosome 3(3q) also occurred in four out of five immortalized cultures. In all cases, structural alterations involving 1q and/or 3q were detected in the primary EGV colonies from which the immortal cell lines arose. Comparison of the frequency of the structural and numerical alterations observed in the immortalized cultures with their frequency in the 29 EGV colonies which did not become immortal indicated that these changes correlated (P less than or equal to 0.005) with the ability to become immortal. These results suggest that structural alterations occur in primary EGV colonies which predispose cells to immortalization and that subsequent numerical changes occur during progression that correlate with acquisition of the immortal phenotype.

Aneuploidy↗

Dual antibody stimulation: role of monocyte products and activation requirements of T cell subsets.

Using the model of dual antibody stimulation (cross-linking anti-CD3 BMA030-F(ab')2 antibodies with subset specific anti-T cell antibodies, i.e., anti-CD4 or anti-CD8 antibodies) we investigated the role of monocyte products in eliciting IL2 production and asked whether T cell subsets differ in their activation requirements. We found that activation mechanisms of dual antibody stimulation were equal for CD4 and CD8 as well as CD4 CDw29 and CD4 CD45R T cell subsets: dual antibody stimulation was necessary to induce responsiveness to soluble monocyte products which trigger IL2 synthesis. IL2 production induced by soluble monocyte products was measured in CD4 and CD8 T cells as specific IL2 mRNA expression and with a biological assay. Combined actions of IL1 beta and TNF alpha were identified as active monocyte products as (a) treatment of LPS-stimulated monocyte supernatants with anti-IL1 beta and anti-TNF alpha antibodies abrogated the proliferation inducing effect of monocyte supernatants and (b) addition of rIL1 beta and/or rTNF alpha enhanced proliferation of T cells stimulated by dual antibody cross-linking. If both recombinant monokines were added simultaneously a potentiated proliferative effect was observed. Whereas rIL1 beta plus/or rTNF alpha sustained proliferation, only rIL1 beta but not rTNF alpha induced IL2 synthesis in T cell subsets stimulated by dual antibody cross-linking.

Antigens, CD↗

Dichotomous effect of monocyte Fc receptor interaction on anti-CD3-induced immunoglobulin synthesis.

Monoclonal antibodies against the TCR/CD3 complex are capable of activating T cells which in turn may induce immunoglobulin synthesis in B cells under appropriate conditions. Here we present evidence that distinct immune responses, induced by four commonly used TCR/CD3 mAb (Leu4, OKT3, BMA030, BMA031) were related to the mAb interaction with monocyte Fc receptors for IgG. Depending on their isotype and on the technique by which they were crosslinked, TCR/CD3 mAb induced variable IgM and IgG synthesis in PBMC: If the mAb were crosslinked by monocyte IgG-Fc receptors they induced a high Ig production, while crosslinking the same mAb by plastic-bound goat anti-mouse antibodies (panning) failed to do so. Nevertheless, both crosslinking techniques triggered a strong proliferation and IL-2, IL-4, and IFN gamma lymphokine gene expression. The lack of Ig production under panning conditions was due to an additional IgG-Fc receptor interaction with monocytes: (a) If namely mAb F(ab')2 fragments, or mAb isotypes unable to bind to monocyte Fc receptors (IgG2b, IgG1 in nonresponders) were crosslinked by panning, both a good proliferation as well as Ig production ensued; (b) if TCR/CD3 mAb isotypes which could additionally bind to monocyte Fc receptor (IgG2a) were crosslinked, no Ig production occurred; (c) if mAb F(ab')2 fragments were crosslinked with a second anti-T cell antibody of IgG2a isotype, which could bind to monocyte Fc receptors, Ig synthesis was reduced. Interestingly enough, this diminishing effect, due to monocyte Fc receptor interaction, was only observed if CD4-positive cells were proliferating, but not if CD8-positive cells were activated.

Adult↗

Expression of growth factor and growth factor receptor RNA in rat pleural mesothelial cells in culture.

Mineral fiber-induced pleural mesothelioma in the rat is a suitable model for asbestos-induced mesothelioma in humans. A proposed mechanism for the genesis of mesotheliomas is the initiation of an autocrine pathway leading to unregulated growth of the mesothelium. To understand if changes in the expression of mRNA of critical growth factors and receptors occur in target mesothelial cells, it is first necessary to characterize the pattern of expression of these genes in normal mesothelial cells. Rat mesothelial cells were isolated from the parietal pleura and strains of these cells were propagated in vitro. The cells were diploid, had epithelial gross morphology and ultrastructure, and coexpressed keratins and vimentin. Northern blot analysis demonstrated that the cells expressed transforming growth factor beta 1 and fibroblast growth factor. Transcripts for transforming growth factor alpha, platelet-derived growth factor A-chain, and platelet-derived growth factor B-chain were not detected. Receptors for platelet-derived growth factor, epidermal growth factor, and insulin were detected. Although normal mesothelial cells express receptors for these growth factors, no production of their corresponding ligands by these cells could be detected, suggesting that autocrine stimulation of growth via the production of such factors may be specific to transformed mesothelial cells.

Animals↗

Pathfinding and synapse formation in a zebrafish mutant lacking functional acetylcholine receptors.

We induced and characterized a recessive lethal mutation, nic-1, in zebrafish that blocks the function of muscle acetylcholine (ACh) receptors. Homozygous nic-1 embryos are nonmotile and fail to respond to exogenous application of cholinergic agonists, although their muscles contract in response to direct electrical stimulation. Moreover, we do not detect cell surface labeling by alpha-bungarotoxin or monoclonal antibodies that recognize the other three subunits of ACh receptors. Motoneurons, however, establish morphologically normal patterns of innervation and normal neuromuscular junctions. We suggest that neither transmitter-mediated nerve signaling nor any other aspect of ACh receptor function is required for the formation of appropriate nerve connections in this system.

Animals↗

Transient diabetes insipidus in pregnancy complicated by hypertension and seizures.

A case is presented of a primigravida with transient diabetes insipidus, gestational hypertension, and multiple seizures resistant to magnesium sulfate and diazepam. After addition of phenytoin, no further seizures occurred. Transient diabetes insipidus in pregnancy has been previously associated with hypertension, liver dysfunction, and fetal distress. Considered with previous cases, it is suggested that seizures may frequently be part of this syndrome.

Adult↗

Measurement of backscatter factors for low energy radiotherapy (0.1-2.0 mm Al HVL) using thermoluminescence dosimetry.

Significant discrepancies of up to 10% exist between backscatter factors (BSF) recommended in a recent IAEA dosimetry Code of Practice (1987) compared with those published in Br. J. Radiol. Supplement 17 (1983), for the x-ray quality range 0.1-2.0 mm Al HVL. In an attempt to resolve this discrepancy, BSFs have been measured using thermoluminescence dosimetry (TLD) with small lithium borate chips, in order to minimise displacement effects associated with the use of larger volume ionisation chambers. Although subject to uncertainties inherent in the TLD calibration and readout process, the results indicate that the BJR (1983) data overestimate BSFs in this quality range. Broad agreement with the IAEA data is indicated, for the limited number of x-ray qualities and field sizes used.

Humans↗

Perforated jejunal diverticulum with multiple hepatic abscesses.

We have described a patient with multiple hepatic abscesses caused by a perforated jejunal diverticulum with a presumed route of infection via the portal vein. Patients with hepatic abscesses and no known source of infection should be evaluated for a contained mesenteric perforation of the gastrointestinal tract. Finally, in patients who fail to respond promptly to percutaneous catheter drainage of a liver abscess, a continuing source of infection, such as perforation of a jejunal diverticulum, should be suspected.

Aged↗

Factors relating to visual acuity in children who have been treated for convergent squint.

Retrospective analysis of a selected sample of children who presented with convergent squint has shown that abnormal meridional hypermetropia (3.5 D or more) at age 1 was the principal factor associated with severe amblyopia (6/24 or less) remaining after conventional treatment. Neither the reported age of onset nor delay in presentation influenced the final visual outcome.

Amblyopia↗

A possible mechanism for the in vitro activation of L-serine deaminase activity in Escherichia coli K12.

L-Serine deaminase is inactive in crude extracts of Escherichia coli K12, but can be activated by incubation with iron and dithiothreitol. This activation requires oxygen, and is inhibited by free radical scavengers and by diethylene triamine pentaacetic acid, which prevents Fe cycling. We suggest that in vitro activation of L-serine deaminase is catalyzed by an oxidant (perhaps hydroxyl radicals). Also, activation may be accompanied by a decrease in molecular weight and involve both a cleavage of the polypeptide chain and a reversible reduction of the molecule.

Antioxidants↗

Placement of balloon-expandable intraluminal stents in iliac arteries: first 171 procedures.

Balloon-expandable intraluminal stents were used to treat iliac artery stenoses or occlusions that failed to respond to conventional balloon angioplasty. One hundred seventy-one procedures were performed in 154 patients, of whom 48 had a limb at risk for amputation. Thirty-six had severe and 70 had moderate intermittent claudication. At the latest follow-up examination (average, 6 months; range, 1-24 months), 137 patients demonstrated clinical benefit, 113 of whom had become asymptomatic. Eleven patients showed no initial benefit, and six improved initially but later developed new vascular symptoms. Complications occurred in 18 patients. In three patients, complications were directly related to the device. Two occlusions were successfully recanalized, and an intramural collection of contrast material secondary to balloon perforation evolved favorably. The remaining patients had groin hematoma (n = 6), distal embolization (n = 4), extravasation (n = 2), transient renal failure (n = 1), pseudoaneurysm at the puncture site (n = 1), or subintimal dissection (n = 1). All stents have remained patent to the latest follow-up examination without evidence of migration or aneurysm formation.

Adult↗

Mutations affecting skeletal muscle myofibril structure in the zebrafish.

We describe embryonic lethal mutations in the zebrafish, Brachydanio rerio, which affect organization of skeletal muscle myofibrils. The mutations, fub-1(b45) and fub-1(b126), were independently isolated from progeny of gamma-irradiated females. Each segregates as a single recessive gene: b45 is located about 23 map units from its centromere. The b126 mutation has a similar but slightly larger apparent gene-centromere distance and a less severe phenotype. The two mutations fail to complement, suggesting that they are allelic. Homozygous b45 mutant embryos are paralyzed, and their axial skeletal muscle cells are unstriated, containing severely disorganized myofibrillar components. Gel-electrophoretic comparisons of b45 mutant and wild-type muscle proteins failed to reveal absent or altered major myofibrillar proteins. Embryos genetically mosaic for b45 were also phenotypically mosaic, suggesting that the defect is cell-autonomous. We suggest that these mutations identify a gene required for proper organization of skeletal muscle myofibrils, and that the more severe mutation may represent a null allele.

Animals↗

Efficacy of clindamycin hydrochloride in refractory periodontitis: 24-month results.

The purpose of this investigation was to evaluate the use of clindamycin hydrochloride in the treatment of adult refractory periodontitis. Thirty patients with a history of unsuccessful treatment with scaling, periodontal surgery, and the use of tetracyclines were entered into the study. Upon entry, the suspected refractory patients were scaled several times and then monitored for the presence of active disease by probing attachment level measurements performed in duplicate. Active disease was defined as a 3.0 mm or greater loss in attachment from the baseline examination or the occurrence of a periodontal abscess. When active disease was detected, patients were treated with scaling and clindamycin 150 mg qid for 7 days. Patients served as their own controls. Twenty four patients demonstrated further attachment loss following scaling alone and were treated with clindamycin hydrochloride. Scaling and clindamycin treatment decreased the incidence of active disease from an annual rate of 8.0% to 0.5% of sites per patient (P less than .001). The mean time required to detect the first active site increased from 4.9 +/- 3.7 months following scaling alone to 16.7 +/- 7.6 months following scaling and clindamycin (P less than 001). Active sites lost an average of 3.1 mm of probing attachment following scaling alone but "gained" back 2.0 mm at 6 months and 1.5 mm at 24 months post-antibiotic and scaling treatment. Bleeding on probing was significantly reduced (P less than .05) from 31.8% of sites pre-clindamycin treatment to 12.3% at 12 months and 17.9% of sites at 24 months post-clindamycin treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The effect of clindamycin on the microbiota associated with refractory periodontitis.

The purpose of this investigation was to determine the effect of clindamycin hydrochloride, as an adjunct to scaling, on the microbiota associated with refractory periodontitis and to elucidate the probable causative bacteria associated with the disease. Microbial samples were collected from a subset of 9 patients with severe adult periodontitis who had not responded to conventional treatment modalities including the use of tetracycline and other antibiotics. Microbial samples were collected from a relatively deep site determined to be actively losing attachment and a comparably deep, but quiescent, control site in each patient prior to clindamycin therapy. Samples continued to be collected from the same sites for up to 1 year post-therapy. The microbial flora of each sample were enumerated by darkfield microscopy and predominant cultivable methods. Prior to clindamycin therapy, both active and control sites consisted on average of approximately 50% spirochetes and motile rods and 40% Gram-negative anaerobic rods. Bacteroides intermedius and Porphyromonas gingivalis (formerly B. gingivalis) were elevated in the active, as compared to control, sites and accounted for approximately 20% of the cultured microbiota in the former. Following treatment with clindamycin, the Gram-negative components of the microbiota were either eliminated or severely suppressed. At 1 year post-therapy, spirochetes and motile rods together accounted for about 15% of the microscopic flora. Total Gram-negative anaerobic rods accounted for approximately 20%, and B. intermedius and P. gingivalis combined accounted for less than 2% of the cultured microbiota from historical active sites.(ABSTRACT TRUNCATED AT 250 WORDS)

Alveolar Bone Loss↗