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C M Sorensen

Publications and source records attributed to C M Sorensen.

At least 19 recordsLinked to original sources
PubMed2000

Role of the renin-angiotensin system in regulation and autoregulation of renal blood flow.

The role for ANG II in renal blood flow (RBF) autoregulation is unsettled. The present study was designed to test the effect of clamping plasma ANG II concentrations ([ANG II]) by simultaneous infusion of the angiotensin-converting enzyme inhibitor captopril and ANG II on RBF autoregulation in halothane-anesthetized Sprague-Dawley rats. Autoregulation was defined as the RBF response to acute changes in renal perfusion pressure (RPP). Regulation was defined as changes in RBF during long-lasting changes in RPP. The results showed that a prolonged reduction of RPP reset the lower limit of autoregulation from 85 +/- 1 to 73 +/- 2 mmHg (P < 0.05) and regulated RBF to a lower level. Reduction of RPP to just above the lower limit of autoregulation (88 mmHg) induced regulation of RBF to a lower level within 10 min. Clamping [ANG II] per se reset the lower limit of autoregulation to 62 +/- 5 mmHg. In this case, reduction in RPP to 50 mmHg did not induce a downregulation of RBF. We conclude that ANG II plays an important role in the resetting of the autoregulation limits. The ability to regulate RBF to a new level as a response to changes in RPP also depends on changes in [ANG II].

Angiotensin II↗
PubMed1994

Neural and biochemical mediators of endotoxin and stress-induced c-fos expression in the rat brain.

We and others have reported that c-fos protein is induced in the hypothalamus and brain stem of the rat following central and peripheral injections of endotoxin (lipopolysaccharide; LPS). We have now examined possible mechanisms through which LPS induces c-fos protein. The cyclooxygenase inhibitor indomethacin and the glutamate NMDA antagonist MK801 inhibited c-fos protein in the paraventricular nucleus (PVN), supraoptic nucleus (SON), and the A1/A2 regions of the brain stem induced by IP or IV injections of LPS (40 micrograms). The H1 histamine antagonist diphenhydramine, but not the H2 histamine antagonist cimetidine, reduced the amount of c-fos labeling. MK801 also attenuated the effects of stress (foot shock) on c-fos protein; however, indomethacin had no effect on c-fos protein induced by stress. We next examined the importance of visceral afferent innervation on the response to LPS or stress. Subdiaphragmatic vagotomy completely blocked the induction of c-fos protein following IP injections of LPS; however, vagotomy had a minimal effect on c-fos protein induced in the PVN and SON following IV injections of LPS, but potentiated c-fos induction following foot shock. Thus, prostaglandin synthesis, glutamate release, histamine receptors, and visceral afferents represent functional biochemical and neural pathways through which endotoxin activates c-fos protein in specific autonomic and neuroendocrine regulatory nuclei. Activation of NMDA glutamate receptors may represent a final common pathway for the induction of c-fos protein in the brain induced by both endotoxin and stress.

Animals↗
PubMed1994

Frequent immunohistochemical detection of EGF supergene family members in ovarian carcinogenesis.

Primary and metastatic ovarian cystadenocarcinomas, carcinomas of low malignant potential (borderline tumors), benign ovarian cystadenomas, and normal ovaries were compared for immunoperoxidase detection of the ligands epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha), amphiregulin (AR), cripto, and the receptors, epidermal growth factor receptor (EGF-R), and c-erbB-2. This matrix analysis of these EGF family members indicated no specific pattern of ligand or receptor expression with a specific ovarian histologic category except in the case of AR and TGF-alpha. AR was detected almost exclusively in borderline tumors, suggesting that these tumors may not arise as a pathological continuum between benign cystadenomas and invasive cystadenocarcinomas. Second, the presence of TGF-alpha immunoreactivity in the absence of coexpression of cripto or EGF appeared to be associated only with adenocarcinomas of high grade and stage.

Amphiregulin↗
PubMed1993

Sizing of bovine heart and kidney pyruvate dehydrogenase complex and dihydrolipoyl transacetylase core by quasielastic light scattering.

Quasielastic light scattering (QELS) measurements on several preparations of bovine heart and kidney pyruvate dehydrogenase complex yielded hydrodynamic radii (rH values) ranging from 25.7 to 30 nm. Gel filtration chromatography removed stable aggregates and generated preparations that gave essentially the same rH values of 24.3 +/- 0.6 nm for both complexes. The data were characteristic of a monodisperse system and agree with estimates using cryoelectron microscopy [Wagenknecht et al. (1991) J. Biol. Chem. 266, 24650-24656]. The equivalent hydrodynamic sizes for the heart and kidney complex indicate that the larger number of pyruvate dehydrogenase components in the heart complex (M(r) congruent to 9 x 10(6)) than the kidney complex (M(r) congruent to 7.5 x 10(6)) associate without radial expansion of the heart complex. That accommodation of additional mass is consistent with the space available since even in the more massive complex greater than 80% of the volume within the dimensions of the complex must be occupied by solvent. Preparations of the core of the complex are primarily composed of 60 dihydrolipoyl acetyltransferase (E2) subunits whose inner domains associate to form a pentagonal dodecahedron that is readily observed by electron microscopy (particle radius 10.7-11.3 nm). However, the bulk of E2's mass is present in an exterior multidomain structure. These mobile outer structures are very difficult to observe by standard electron microscopy techniques. Preparations of the core formed stable aggregates that were removed by gel filtration chromatography. QELS measurements gave an rH of 20.1 +/- 0.8 nm.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetyltransferases↗
PubMed1993

Differential induction of c-Fos immunoreactivity in hypothalamus and brain stem nuclei following central and peripheral administration of endotoxin.

Lipopolysaccharide (LPS), an endotoxin associated with gram-negative bacteria, is a potent activator of the immune system. We have tested the effects of ICV infusions of LPS (10 ng) or Ringer's solution on the induction of the proto-oncogene protein c-Fos in the brain as well as plasma levels of corticosterone and splenic concentrations of norepinephrine (NE) and VIP. At 3 h post-ICV infusion of LPS, numerous labeled neurons were observed in the paraventricular nucleus (PVN) of the hypothalamus and the nucleus tractus solitarius (A2) region of the brain stem. Also, corticosterone and splenic NE and VIP levels were all elevated post-ICV LPS. Analysis of the time course for the induction of c-Fos protein in the brain following IP injections of LPS indicated that, relative to control injections, increased numbers of c-Fos-positive cells were detected in the PVN 0.5 h following IP injections (100 micrograms), peaked at 2-3 h postinjection, and then returned to control levels at later intervals. Additional dose-response data for IP LPS indicated a small increase in the number of labeled cells at a dose of 4.0 micrograms, and the number and staining intensity increased up to a dose of 100 micrograms. Corticosterone levels followed a similar pattern and were elevated at the 4.0 micrograms IP dose of LPS and increased to peak levels at 40 micrograms and higher. In contrast to ICV injections, splenic NE levels were unaltered by IP injections of LPS.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Growth factor expression during rat development: a comparison of TGF-beta 3, TGF-alpha, bFGF, PDGF and PDGF-R.

At least part of the mechanism underlying fetal development appears to be the production of a number of growth factors considered important in the process of tumour formation. Using immunocytochemistry, we have investigated the temporal and spatial pattern of expression of some of the important growth factors, by the fetus. We describe here the cellular localization of transforming growth factor beta 3 (TGF-beta 3), platelet derived growth factor (PDGF) and its receptor (PDGF-R), TGF-alpha and basic fibroblast growth factor (bFGF) in the fetal rat from day 13 to 21 of gestation. Using antisera raised against an N-terminal portion of TGF-beta 3, immunoreactivity peaked around day 16 and was seen predominantly within epithelial cells. However, using antisera raised against the C-terminal of this molecule immunoreactivity was seen exclusively within the extracellular matrix underlying adjacent epithelia, and was maintained up until day 21 of gestation. Strong expression of TGF-alpha was seen in cells of most organs throughout the gestation period studied. Immunoreactivity for bFGF, PDGF and PDGF-R peaked around day 18 in both epithelial and mesenchymal cells of all major organ systems and then declined by day 21. These data suggest distinct roles for each factor during embryogenesis and tumorigenesis.

Animals↗
PubMed1991

Bcl-2 maintains B cell memory.

The number of lymphocytes in an animal is remarkably constant despite antigen-driven proliferation and a high rate of B-cell lymphopoiesis. This reflects the relatively brief lifespan of many newly generated B cells and argues for a well-regulated death mechanism. Even so, a secondary immune response can be generated years after a primary exposure to antigen. Antigen that might restimulate B cells persists for extended periods on follicular dendritic cells in the light zone of germinal centres. Antigen-binding B cells have also been found months after the end of obvious cell division. The precise signal that enables certain B cells to emerge as long-term surviving memory cells is unknown. Bcl-2, an inner mitochondrial membrane protein, blocks programmed cell death in B cells. We report here that this proto-oncogene maintains immune responsiveness. Transgenic mice overproducing Bcl-2 have a long-term persistence of immunoglobulin-secreting cells and an extended lifetime for memory B cells.

Animals↗
PubMed1988

Identification of suppressor T cells in virgin non-responder spleen cells responsible for primary unresponsiveness to L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT).

T cell subsets that regulate antibody responses to L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT) in mice that are Ir gene non-responders have been further characterized. We previously defined several T cell subsets in GAT-primed non-responder mice. The Lyt-2+ suppressor-effector T cells suppress responses to GAT and GAT complexed to methylated BSA (GAT-MBSA). The Lyt-1+ cell population is complex and can be separated into I-J- Th cells, which support responses to GAT and GAT-MBSA. After priming, the Lyt-1+, I-J+ cell population contains suppressor-inducer cells that activate precursors of suppressor-effector cells to suppress responses to GAT and GAT-MBSA as well as Ts cells that directly inhibit responses to GAT but not GAT-MBSA. By contrast, the Lyt-1+ cells from virgin mice contain only cells that directly suppress responses to GAT but not GAT-MBSA. The major question addressed in the present studies was whether the Lyt-1+, I-J+ Ts cells in virgin and primed mice and the suppressor-inducer cells in GAT-primed mice were functionally and serologically distinct subsets. The studies used mAb and panning procedures to separate cell populations and inhibition of PFC cell responses to functionally define the activity of the cell populations. We used the following two mAb that were raised by immunizing rats with GAT-specific suppressor factors: 1248A4.10 (known to react with suppressor-inducer cells) and 1248A4.3, another reagent from the same fusion. Lyt-1+ cells from virgin spleens contained Ts cells that were A4.10-, A4.3+ and no suppressor-inducer T cells, whereas Lyt-1+ cells from GAT-primed spleens contained Ts cells that were A4.10-, A4.3+ as well as A4.10+, A4.3- suppressor-inducer cells. Thus, the Lyt1+, I-J+ cell subset can be divided into two functionally and serologically distinct subsets, direct Ts cells (1248A4.3+), which suppress responses to GAT but not GAT-MBSA, and GAT-primed suppressor-inducer T cells (1248A4.10+).

Animals↗
PubMed1987

Molecular genetic characterization of the mRNA coding for an inducible suppressor factor specific for L-glutamic acid60-L-alanine30-L-tyrosine10.

The suppressor T-cell hybridoma 1556A2.1 can be induced by the monoclonal L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT)-specific suppressor inducer 372B3.5 and soluble GAT to synthesize a disulfide-linked heterodimeric protein (GAT-TsF2), which directly suppresses a primary in vitro immune response to GAT. Induction and synthesis of the GAT-TsF2 protein is correlated with the appearance of specific mRNA, as detected by translation in vitro in a wheat germ cell-free extract of RNA isolated at various times after induction. The mRNA coding for the polypeptide chain that bears a serologically defined I-J determinant (I-J+ chain) appeared 8 hr after induction, whereas the mRNA coding for the antigen-binding chain (AB+ chain) was not detected until 16 hr after induction. The mRNAs coding for the individual chains sedimented as different species, suggesting that the two-chain factor is the product of two genes. The AB+ chain of the 1556A2.1 GAT-TsF2 was synthesized on membrane-bound polysomes, whereas the I-J+ chain was translated on free polysomes. The AB+ chain was synthesized from two independent mRNA species sedimenting at 10 S and 28 S, whereas a single 16S mRNA encoded the I-J+ chain. The in vitro translated I-J+ chain was bound by a monoclonal antibody against the I-J+ determinant of only the appropriate H-2 haplotype. These results suggest that posttranslational modification, including glycosylation, is not required for biological activity or for expression of the I-J epitope on the GAT-TsF2 molecule.

Animals↗
PubMed1986

Characterization of two monoclonal idiotype-binding suppressor T cell factors specific for the antibody response to L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT).

We have previously identified and described two distinct types of suppressor T cell factors specific for the PFC response to L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT) or L-glutamic acid50-L-tyrosine50 (GT). Both of these factors are antigen-specific and I-J+. GAT-TsF1 is not MHC-restricted and is composed of a single polypeptide chain, whereas GAT-TsF2 is MHC-restricted and is composed of two different polypeptide chains. We have not previously found evidence for an obligatory, idiotype-specific suppressor T cell in this suppressor pathway. However, we now report that idiotype-specific suppressor T cells can be elicited by exposing normal spleen cells to GAT-TsF1 or GAT-TsF2 in the absence of antigen in vitro. These factor (TsF1/TsF2)-induced cells have been fused with the AKR thymoma, BW5147, and hybridomas were selected for production of suppressor factors that inhibit GAT-specific antibody responses in vitro. In this report, we characterize one monoclonal factor from each fusion. Neither factor binds GAT or the related co-polymer, GT; both factors have binding sites for GAT-specific idiotypes but not for unrelated idiotypes either in the form of antibody immobilized on Sepharose or as cell surface determinants expressed by B cell hybridomas. Moreover, their reactivities for a panel of monoclonal anti-GAT antibodies are overlapping but not identical. Both factors are composed of two polypeptide chains, and both chains are required for suppressive activity; one chain bears the I-J determinant, whereas the other possesses the idiotype-binding activity of the intact molecule. Both idiotype-binding factors are restricted by MHC- and Igh-linked genes, and transcomplementation is observed in the F1 mice between MHC-congenic and Igh-congenic parents. Both factors are active late in Mishell-Dutton cultures. These data support the contention that these two factors are similar but nonidentical members of an anti-idiotypic class of GAT-specific suppressor factors.

Animals↗
PubMed1986

Identification and characterization of a suppressor T cell hybridoma specifically inducible by L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT).

In vitro activation of naive spleen cells from C57BL/10 mice with GAT and the monoclonal GAT-TsF1, 372B3.5, followed by fusion with BW5147 resulted in generation of a hybridoma that fails to produce GAT-TsF constitutively, but upon reexposure to GAT and 372B3.5 is induced to secrete GAT-TsF2. The induction is GAT specific and requires de novo RNA, protein synthesis, and DNA synthesis. Although both GAT and 372B3.5 are required for induction, they may be added sequentially, provided the GAT is added first. The GAT-TsF produced by the induced cell is antigen specific and composed of two polypeptide chains: one capable of binding antigen, the other bearing determinants encoded by the I-J region of the MHC. The utility of this inducible GAT-TsF2 cell line for molecular biology and other studies is discussed.

Animals↗
PubMed1986

Cellular interactions of L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT)-specific suppressor factors. I. Inhibition of the activity of GAT-specific helper T cell clones by monoclonal GAT-specific suppressor T cell factors.

Considerable information concerning the serology and biochemistry of antigen-specific, T cell-derived suppressor factors has been obtained with the use of T cell hybridomas as a source of homogeneous material. Similarly, knowledge of helper T cell products and receptors is accumulating from studies of helper T cell clones and hybridomas. Our strategy for studying the mechanisms by which suppressor factors inhibit responses was to determine whether monoclonal suppressor factors could inhibit antibody responses specific for L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT) in cultures containing unprimed splenic B cells, macrophages, and GAT-specific T cell clones as a source of helper activity. The MHC-restricted, two chain suppressor factors, GAT-TsF2, inhibited these responses if the helper T cell clones and suppressor factor were derived from H-2-compatible mice. Furthermore, responses were inhibited by briefly pulsing T cell clones with GAT-TsF2 in the presence of GAT, indicating that suppressor factors need not be present continuously. In addition, helper T cell clones adsorbed syngeneic, but not allogeneic, GAT-TsF2 in the presence of GAT. Adsorption also requires a shared antigenic specificity between the H-2b-derived helper T cells and TsF2 factor. Thus, helper T cells can serve as the cellular target of antigen-specific, MHC-restricted GAT-TsF2, and cloned helper T cells can be used as a homogeneous target population for analysis of the molecular mechanisms of T cell suppression.

Adsorption↗
PubMed1985

Identification of Igh-C-linked determinants on suppressor T cell hybrids and factors specific for L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT).

Hyperimmunization of BALB/c mice with concanavalin A-stimulated blasts from the Ig allotype-congenic strain, C.B20, results in the production of antibodies reactive with T cells in an allotype-restricted manner. Spleen cells from these hyperimmune BALB/c mice were used to generate a panel of hybridomas that secrete monoclonal antibodies, reactive, in an allotype-restricted manner, exclusively with T cells subpopulations, and in particular, reactive with suppressor T cell hybridomas and their secreted soluble factors. Two functional classes of antibodies were identified: those that react with single polypeptide-chain suppressor T cell factors (TsF1) and the suppressor T cell hybridomas that produce such factors, and those that react with two polypeptide-chain suppressor T cell factors (TsF2) and their corresponding suppressor T cell hybridomas. These two classes of antibody were used to isolate molecules from the membranes of the respective suppressor T cell hybrids that are functionally and structurally related to the secreted suppressor T cell factors, suggesting a receptor function for these molecules.

Animals↗