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C Hopkins

Publications and source records attributed to C Hopkins.

16 recordsLinked to original sources
PubMed1992

Monoclonal antibodies against defined epitopes of the human transferrin receptor cytoplasmic tail.

Three murine monoclonal antibodies (mAbs) against the 61-residue amino-terminal cytoplasmic tail of the human transferrin receptor (TR) have been produced by immunization of mice with recombinant human TR produced in a baculovirus expression system. Mutant human TRs expressed in chick embryo fibroblasts (CEFs) with point mutations or deletions in their cytoplasmic tails have been used to map the epitopes defined by each of the mAbs. One mAb, H68.4, previously shown to block receptor internalization, binds proximal to the carboxy-terminal side of the YTRF internalization signal of TR. The second mAb, H73.2, binds near to the carboxy-terminal side of the H68.4 epitope, whereas the third mAb, 160.1, binds closer to the transmembrane region. H68.4 and H73.2 are auto-antibodies consistent with their epitopes mapping to a region of the human TR that has an identical amino acid sequence to the mouse TR. All three mAbs crossreact with the cytoplasmic tail of Chinese hamster TR. Double labelling of recombinant human TRs on chick embryo fibroblast (CEF) cell membrane preparations with B3/35 and H68.4 antibody-gold conjugates established that receptors in clathrin-coated pits were not labeled with H68.4, implying that associated coated pit proteins may block binding of this mAb.

Amino Acid Sequence↗
PubMed1990

Role of the human transferrin receptor cytoplasmic domain in endocytosis: localization of a specific signal sequence for internalization.

Wild-type and mutant human transferrin receptors have been expressed in chicken embryo fibroblasts using a helper-independent retroviral vector. The internalization of mutant human transferrin receptors, in which all but four of the 61 amino acids of the cytoplasmic domain had been deleted, was greatly impaired. However, when expressed at high levels, such "tailless" mutant receptors could provide chicken embryo fibroblasts with sufficient iron from diferric human transferrin to support a normal rate of growth. As the rate of recycling of the mutant receptors was not significantly different from wild-type receptors, an estimate of relative internalization rates could be obtained from the distribution of receptors inside the cell and on the cell surface under steady-state conditions. This analysis and the results of iron uptake studies both indicate that the efficiency of internalization of tailless mutant receptors is approximately 10% that of wild-type receptors. Further studies of a series of mutant receptors with different regions of the cytoplasmic domain deleted suggested that residues within a 10-amino acid region (amino acids 19-28) of the human transferrin receptor cytoplasmic domain are required for efficient endocytosis. Insertion of this region into the cytoplasmic domain of the tailless mutant receptors restored high efficiency endocytosis. The only tyrosine residue (Tyr 20) in the cytoplasmic domain of the human transferrin receptor is found within this 10-amino acid region. A mutant receptor containing glycine instead of tyrosine at position 20 was estimated to be approximately 20% as active as the wild-type receptor. We conclude that the cytoplasmic domain of the transferrin receptor contains a specific signal sequence located within amino acid residues 19-28 that determines high efficiency endocytosis. Further, Tyr 20 is an important element of that sequence.

Amino Acid Sequence↗
PubMed1989

Dusts causing pneumoconiosis generate .OH and produce hemolysis by acting as Fenton catalysts.

Silicates causing pneumoconiosis function as Fenton catalysts to generate hydroxyl radicals (.OH) when incubated with hydrogen peroxide and a reducing substance. In contrast, silicates which do not cause pneumoconiosis demonstrate no Fenton activity. Catalytic activity is decreased by pretreatment of silicates with the iron chelators deferoxamine or transferrin. Hemolysis from silicates is decreased by interventions which remove superoxide anion or hydrogen peroxide from the medium, or by pretreatment of dusts with iron chelators. Thus, asbestos and nonfibrous silicates may cause pneumoconiosis through a common oxidant mechanism by catalyzing production of toxic .OH radicals in the lung.

Catalysis↗
PubMed1989

Dibutyryl cAMP, aminophylline, and beta-adrenergic agonists protect against pulmonary edema caused by phosgene.

Phosgene is a toxic oxidant gas that causes the adult respiratory distress syndrome in exposed workers. Phosgene exposure markedly increased lung weight gain in buffer-perfused isolated rabbit lungs (31 +/- 5 g over 60 min after phosgene vs. 7.7 +/- 1.2 in control lungs, P less than 0.01) and markedly increased the lung leak index for 125I-albumin (0.28 +/- 0.03 after phosgene vs. 0.02 +/- 0.01 in control lungs, P less than 0.01). Pretreatment with dibutyryl adenosine 3',5' -cyclic monophosphate (DBcAMP), aminophylline, or terbutaline plus isoproterenol prevented the increase in lung weight caused by phosgene (31 +/- 5 g phosgene, 11.7 +/- 2.8 DBcAMP, 7.5 +/- 2.5 aminophylline, 6.1 +/- 1 terbutaline and isoproterenol, 6.1 +/- 1.2 control + aminophylline, and 7.7 +/- 1.2 control; all treatments were P less than 0.01 vs. the untreated phosgene group and not significantly different from control lungs). Pretreatment with aminophylline prevented the increase in lung leak index for 125I-albumin (0.28 +/- 0.03 after phosgene vs. 0.06 +/- 0.02 in aminophylline-treated lungs, P less than 0.01). Posttreatment with aminophylline and terbutaline also prevented the increase in lung weight caused by phosgene. These results indicate that phosgene dramatically increases the movement of fluid and protein across the pulmonary vasculature and that treatment with DBcAMP, aminophylline, terbutaline, or isoproterenol markedly reduces the pulmonary edema caused by phosgene.

Aminophylline↗
PubMed1989

Role of reactive oxygen species in reperfusion injury of the rabbit lung.

We have developed a model of reperfusion injury in Krebs buffer-perfused rabbit lungs, characterized by pulmonary vasoconstriction, microvascular injury, and marked lung edema formation. During reperfusion there was a threefold increase in lung superoxide anion (O2-) production, as measured by in vivo reduction of nitroblue tetrazolium, and a twofold increase in the release of O2- into lung perfusate, as measured by reduction of succinylated ferricytochrome c. Injury could be prevented by the xanthine oxidase inhibitor allopurinol, the O2- scavenger SOD, the hydrogen peroxide scavenger catalase, the iron chelator deferoxamine, or the thiols dimethylthiourea or N-acetylcysteine. The protective effect of SOD could be abolished by the anion channel blocker 4,4'-diisothiocyano-2,2'-stilbene disulfonic acid, indicating that SOD consumes O2- in the extracellular medium, thereby creating a concentration gradient favorable for rapid diffusion of O2- out of cells. Our results extend information about the mechanisms of reperfusion lung injury that have been assembled by studies in other organs, and offer potential strategies for improved organ preservation, for treatment of reperfusion injury after pulmonary thromboembolectomy, and for explanation and therapy of many complications of pulmonary embolism.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1988

Do nigro-striatal neurones possess a discrete dendritic modulatory mechanism? Electrophysiological evidence from the actions of amphetamine in brain slices.

Dopamine released from dendrites of nigrostriatal neurones in the substantia nigra exerts an inhibitory action on these cells. However, the spatio-temporal characteristics of the action of dendritic dopamine is still unclear. The aim of the present study was to investigate the responses of these neurones in the guinea-pig to amphetamine, applied locally in the region of the distal dendrites in pars reticulata. During intracellular recording in vitro it was found that amphetamine hyperpolarizes the membrane and causes a decrease in the input resistance, probably by increasing a potassium conductance. This response was resistant to blockade of sodium channels but sensitive to dopamine depletion by reserpine and alpha-methyl-p-tyrosine. The response showed tachyphylaxis and proved to be highly dependent on the site of administration of amphetamine. It is concluded that the release and action of dopamine occurs locally, in a heterogeneous pattern, within the dendritic field of nigrostriatal neurones. The possibility is discussed that this phenomenon underlies a modulatory mechanism, localized in dendrites.

Action Potentials↗
PubMed1987

Localisation of the protein and glycoprotein components of bovine nasal epithelial desmosomes by immunoelectron microscopy.

Desmosomal proteins (dp1-4) and glycoproteins (dg1-3) have been localised within desmosomes of bovine nasal epithelium by immunogold labelling of ultrathin frozen sections. Beginning in the extracellular space and proceeding through the plaque to the tonofilaments, the following localisations were found. Labelling for the 130,000 and 115,000 Mr glycoproteins (dg2 and dg3) was predominantly in the extracellular space, a location consistent with their proposed adhesive function. The glycoproteins of 175,000-164,000 Mr (dg1) were also found in the extracellular space and in addition had cytoplasmic domains extending throughout the cytoplasmic plaque. The 83,000 Mr protein (dp3) was located along the cytoplasmic face of the membrane and extended into the plaque, whereas an antibody which recognises both the 83,000 Mr protein (dp3) and the 75,000 Mr protein (dp4) gave labelling both in and beyond the plaque. Labelling for the high mol. wt proteins of Mr 250,000 and 215,000 (dp1 and dp2) was largely excluded from the plaque, and was located distally, adjacent to the tonofilaments. Hemidesmosomes could not be labelled with antibodies to dg1-3 or dp3 and 4, but some labelling was obtained with antibody to dp1 and 2.

Animals↗
PubMed1977

Effects of ultrafiltration on solute clearances in parallel plate dialyzers.

Clearances of small and large solutes were measured at increasing transmembrane pressure in 3 types of parallel plate dialyzers. Both laboratory and clinical studies were performed. As in previously reported studies in coils, diffusive transport appears to decrease as transmembrane pressure increases. This may reflect blood channel widening, bath channeling, and/or membrane masking by mesh support. For small solutes, decreases in diffusive transport were enough to offset gains by solvent drag and total clearances decreased. In some studies, decreases in small solute clearances with increasing ultrafiltration were large enough to compromise dialysis efficiency.

Diffusion↗
PubMed1974

What's to hear.

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Environmental Pollution↗
PubMed1973

Health education.

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Arkansas↗
PubMedDate not supplied

A family practice model of health care for homeless people: collaboration with family nurse practitioners.

The growth of a large population of people without permanent housing in the United States has brought with it the necessity to address the unmet health needs of this group. As homelessness spreads, its demographic pattern has become more heterogeneous, with young vulnerable families now the major subgroup. This paper explores issues of homelessness in Westchester County, N.Y., which, despite being the 10th richest county in the United States, has the highest per capita homeless rate in the state. Children younger than age 18 represent the majority of this group. Barriers to the delivery of health care services are described, including fragmented life-styles, lack of insurance, insensitivity of care givers, distance from services, and inflexibility of traditional sources of health care. A model that has been developed for delivery of services is discussed. This model, the Outreach Health Care Unit, is run by nurse practitioners in collaboration with family physicians and is centered at the site of social service activities for homeless families and single men in Yonkers, N.Y. It is a collaborative endeavor of a nursing school, community hospital family practice residency program, and a network of social service agencies. The use of this model for education and research is also discussed since the goal is to provide both health services and training for health care providers.

Adolescent↗