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Biomedical subjects

R Carroll

Publications and source records attributed to R Carroll.

At least 91 records · Page 5Linked to original sources
PubMed1991

Identification of lentivirus tat functional domains through generation of equine infectious anemia virus/human immunodeficiency virus type 1 tat gene chimeras.

The structural regions that comprise the functional domains of lentivirus Tat proteins were examined. Chimeric tat genes and chimeric viral promoters were constructed between the distantly related human immunodeficiency virus type 1 (HIV-1) and equine infectious anemia virus (EIAV). These exchange experiments revealed that the EIAV Tat-responsive element recognition domain is formed by two distinct structural regions. Activation domains of both HIV-1 and EIAV Tat contain a conserved core element, but at least HIV-1 Tat requires the presence of additional structural regions. The interchangeable nature of Tat activation domains suggests that these domains act through a common or ubiquitous cellular transcription factor.

Amino Acid Sequence↗
PubMed1991

Recurrent ovarian carcinoma: presentation as idiopathic thrombocytopenic purpura and a splenic mass.

We report a case of a 38 year old female who was treated for a Stage IIIb serous cystadenocarcinoma of the ovary with cytoreduction, combination chemotherapy, negative second look laparotomy, and adjuvant chemotherapy, who eight months later presented with Idiopathic Thrombocytopenic Purpura (ITP) and an isolated splenic recurrence. Review of the literature shows only four other cases of gynecologic malignancy which exhibited this pattern of recurrence. This case is the first where the primary lesion was an ovarian carcinoma and the patient presented with thrombocytopenia.

Adult↗
PubMed1990

Treatment of cardiac myocytes with 8-(4-chlorophenylthio)-adenosine 3',5'-cyclic monophosphate, forskolin or cholera toxin does not stimulate cellular or heparin-releasable lipoprotein lipase activities.

Incubation of isolated cardiac myocytes with 500 microM-8-(4-chlorophenylthio)adenosine 3',5'-cyclic monophosphate (CPT-cAMP) or 100 microM-forskolin for 2 1/2 h did not increase the heparin-induced release of lipoprotein lipase (LPL) into the medium. When LPL activity in cardiac myocytes was depleted by treatment of rats with cycloheximide (2 mg/kg; 2.5 h) and inclusion of the protein-synthesis inhibitor in the isolation solutions, incubation with CPT-cAMP or forskolin did not influence the rate of repletion of LPL activity in cells or the recovery of heparin-releasable LPL activity. Although the administration of cholera toxin (0.5 mg/kg; 16-17 h) to rats increased LPL activity in a low-speed supernatant fraction from heparin-perfused hearts, LPL activity was not increased in cardiac myocytes from cholera-toxin-treated rat hearts, and the heparin-induced release of LPL was unchanged. Incubation of cultured ventricular myocytes with 1 microgram of cholera toxin/ml or 500 microM-CPT-cAMP for 24 h did not increase cellular LPL activity or LPL released into the culture medium after a 40 min incubation with heparin. Therefore interventions that stimulate adenylate cyclase activity (forskolin, cholera toxin) or incubation with CPT-cAMP do not increase cellular LPL activity or promote the translocation of LPL to a heparin-releasable fraction in cardiac myocytes.

Animals↗
PubMed1990

Improved detection of the histamine receptor on human peripheral blood mononuclear cells by crosslinking using tritiated as compared with radioiodinated histamine.

In order to detect histamine receptors on the surface of human peripheral blood mononuclear cells, the cells were incubated in the presence of radiolabelled histamine and then the bifunctional crosslinker disuccimidyl suberate was added in various concentrations. They were then solubilized with sodium dodecyl sulphate, boiled, reduced and the lysate separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Both 3H and 125I-radiolabelled ligands bound to a 16 kDa band, to be defined although a much clearer and obviously unequivocal signal was obtained with 3H-labelled histamine. This molecule migrated with the same mass on sodium dodecyl sulfate-polyacrylamide gel electrophoresis as a 16 kDa subunit which had been purified on a histamine affinity column from Triton X-100 solubilized mononuclear cells, indicating it to be the ligand-binding subunit for the histamine receptor on these cells. For 3H, fluorography with Entensify was required to obtain an autoradiographic signal. Although 3H took much longer to give a signal than 125I, the considerable background, artefacts and heavy lane trailing seen with [125I] histamine were completely abrogated when [3H]histamine was used. In addition, the distinction between specific and nonspecific binding was more clearly seen using [3H]histamine. The modifications reported here which improve signal detection for 3H should encourage the use of tritiated ligands in radioreceptor crosslinking, particularly those of low molecular weight which might otherwise undergo steric modification due to iodination, this having the potential for interfering with receptor ligand binding.

Autoradiography↗
PubMed1990

The immunosuppressive action of FK506. In vitro induction of allogeneic unresponsiveness in human CTL precursors.

FK506 is an unusually potent new immunosuppressive agent that inhibits T cell-mediated immunity in vivo and in vitro. In these studies we sought to further elucidate the immunosuppressive mechanism of action of FK506 on human allogeneic MLR-induced CTL activation. FK506 induced suppression of cell-mediated lympholysis by PBMC was optimal at 1-2-nM concentrations, if added at the initiation of 6 day CML cultures. The sensitivity to suppression decreased with time, and fully differentiated effectors were resistant to inhibition by FK506. Suppression of CML was not reversed by washing the cultures, adding exogenous IL-2, or restimulating with fresh cells. Pretreatment of unfractionated or adherent allogeneic PBMC with FK506 blocked the stimulating activity of these cells. Furthermore, addition of FK506-treated stimulator cells to cocultures containing untreated responder and stimulator cells resulted in suppression of CML. The inhibition in the cocultures was greatest if the FK506-pretreated cells were autologous to the original stimulator, suggesting a relative specificity in the suppression obtained under these conditions. These studies suggest that, in addition to suppressing the response of alloreactive CTL precursors, FK506 reduces the ability of irradiated allogeneic PBMC to induce CTL generation.

Anti-Bacterial Agents↗
PubMed1990

Apolipoprotein VLDL-II inhibits lipolysis of triglyceride-rich lipoproteins in the laying hen.

In the laying hen, very low density lipoprotein (VLDL) particles contain large amounts of apolipoprotein (apo)-VLDL-II in addition to apoB. These triglyceride-rich lipoproteins are transported from the liver primarily to growing oocytes. Since no appreciable hydrolysis of triglyceride occurs during this transport, we have investigated the possibility that apoVLDL-II functions as an inhibitor of lipoprotein lipase (LPL). The presence of LPL in chicken follicular granulosa cells was demonstrated by immunoblotting, and LPL activity with the usual in vitro characteristics could be measured in cultured granulosa cell extracts. ApoVLDL-II inhibited LPL activity in these extracts as well as in the post-heparin medium of rat cardiac myocytes. Half-maximal inhibition in both systems occurred at 40 micrograms/ml, a concentration that is one-tenth of the circulating apoVLDL-II in the laying hen. Much less inhibition was observed with reduced and alkylated apoVLDL-II and with apoA-I. We conclude that the presence of apoVLDL-II on laying hen VLDL ensures efficient delivery of triglyceride to the oocyte for subsequent use as energy source by the embryo.

Animals↗
PubMed1989

Isolation and characterization of a 50 kDa testosterone-binding protein from Pseudomonas testosteroni.

A testosterone-binding protein (Mr = 50,500) has been isolated from the Gram-negative bacterium Pseudomonas testosteroni. The protein was partially purified by a combination of ion exchange chromatography and chromatofocusing. Final purification was achieved by electroelution of the 50 kDa protein from SDS-polyacrylamide gels. Following renaturation from a diluted solution of guanidine-HCl, specific binding of [3H]testosterone to the purified protein was observed. The native protein has a pI of 6.8. It appears to contain 428 amino acids, 39% of which are hydrophobic. There is only one cysteine residue. Both chymotrypsin and V8 protease were used to produce peptide maps of the protein for use in future identification. The first 10 amino acids situated at the N-terminal of the protein were Ser-Pro-Phe-Asp-Leu-Arg-Pro-Leu-Ser-Gly. Testosterone binding to the protein was saturable at approximately 3.8 nmol/mg protein; the binding constant was approximately 25 nM. Unlabelled testosterone, androstenedione, 5 alpha-dihydrotestosterone and 5 beta-dihydrotestosterone were able to compete for [3H]testosterone bound to the protein; 17 beta-estradiol also competed for [3H]testosterone but to a lesser degree. Neither progesterone nor desoxycorticosterone competed for the testosterone-binding site. Binding of testosterone to the protein was stable at pH's ranging from 5.5 to 9.0 and at various temperatures ranging from 4 to 30 degrees C. The protein was unable to metabolize testosterone in either the presence or absence of the cofactor NAD.

Amino Acids↗
PubMed1989

Neurovisual outcome following proton radiation therapy.

From February 1981 to January 1984, 20 patients with a tumor of the upper clivus received proton irradiation at the Harvard Cyclotron Laboratory. For 15 patients with known neurovisual status (including visual acuity, color vision, visual field, and fundus examinations) we obtained a cumulative dose-volume histogram (DVH) of the optic nerves (ON) and the optic chiasm. The prescribed tumor doses ranged from 66.6 to 74.4 Cobalt Gray Equivalent (CGE) with a daily fraction size of 1.8 to 2.1 CGE. CGE is used because modulated protons have an RBE of 1.1 compared to 60Co. The follow-up ranged from 30 to 68 months (median 52). Two patients developed, 10 and 36 months post irradiation, a progressive visual deterioration affecting both eyes. This was attributed to an ON and a chiasm injury in one patient and to bilateral ON injury in the other patient. In the first patient, the dose-volume analysis indicated that approximately half of the ON and of the chiasm had received 65 CGE and 55 CGE, respectively. In the second patient, it indicated that a quarter of the left ON (LON) had received 55 CGE whereas the dose to the right ON (RON) was significantly less. This patient had diabetes mellitus which may be a predisposing factor. From this study, a complication rate of 20% (1/5) is observed when a substantial portion of the ON is taken to 65 CGE, while it doesn't exceed 12.5% (2/16) and 7.5% (1/13) at 55 CGE for the ON and for the chiasm, respectively. This suggests a tolerance dose implying a 10% rate of major complications close to 55 CGE. When a tumor requires a high radiation-dose, the exclusion of these structures at 55 to 60 Gy is recommended.

Adult↗
PubMed1989

Selective detection of human papilloma virus DNAs by specific synthetic DNA probes.

Specific oligodeoxynucleotide probes ranging from 20 to 35 nucleotides were defined to differentiate each of the HPV1a, 5, 6b, 8, 11, 16, 18 and 33. They were chosen using computer programs developed to compare simultaneously several 8000 bp long DNA sequences. Sequences common to all and to specific groups of the HPV DNA were also selected. Specificity of 32P-labelled probes for HPV6b, 11, 16, 18 and 33 was demonstrated and the sensitivity of the assays was evaluated by filter hybridization with viral clones and with DNA from cervical tumor biopsies.

Base Sequence↗
PubMed1988

Secretion of lipoprotein lipase from myocardial cells isolated from adult rat hearts.

Heparin (5 U/ml) induced the release of LPL into the incubation medium of cardiac myocytes isolated from adult rat hearts. The secretion of LPL occurred in two phases: a rapid release (5-10 min of incubation with heparin) that was independent of protein synthesis followed by a slower rate of release that was inhibited by cycloheximide. The rapid release of LPL induced by heparin likely occurs from sites that are at or near the cell surface. LPL secretion could also be stimulated by heparan sulfate and dermatan sulfate, but not by hyaluronic acid, chondroitin sulfate or keratan sulfate. Heparin-releasable LPL activity measured in short-term incubations represented a large fraction (40-50%) of the initial LPL activity associated with myocytes, but the fall in cellular LPL activity following heparin was less than the amount of LPL activity secreted into the incubation medium. This discrepancy was not due to latency of LPL in the pre-heparin cell homogenates, but in part could be due to a three-fold greater affinity of the heparin-released enzyme for substrate as compared to LPL in post-heparin myocyte homogenates.

Animals↗
PubMed1988

Eicosanoid synthesis in 7,12-dimethylbenz(a)anthracene-induced mammary carcinomas in Sprague-Dawley rats fed primrose oil, menhaden oil or corn oil diet.

The comparative effects of high-fat diets (20%, w/w) on eicosanoid synthesis during mammary tumor promotion in 7,12-dimethylbenz(a)anthracene (DMBA)-induced rats were studied using diets containing 20% primrose oil (PO), 20% menhaden oil (MO) or 20% corn oil (CO). Sprague-Dawley rats fed the PO or MO diet had 21% of 24% fewer adenocarcinomas, respectively, than rats fed the CO diet. Histologically (i.e., mitotic figures, inflammatory cell infiltration and necrosis), the CO-fed rats exhibited the highest frequency of changes within tumors. Plasma fatty acid composition was significantly altered by diet, reflecting the composition of the oils which were being fed. Only the plasma of PO-fed rats contained detectable levels of gamma-linolenic acid (GLA). Arachidonic acid (AA) levels were significantly higher (p less than 0.05) in PO-fed than in CO- or MO-fed rats. MO-fed rats had significantly higher levels of plasma palmitic acid, while palmitoleic, eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids were detected only in MO-fed rats. As expected, linoleic acid (LA) and AA levels were lower (p less than 0.05) in the MO-fed rats than in PO- or CO-fed groups. The plasma of the CO-fed rats contained significantly higher levels of oleic acid. Eicosanoid synthesis in mammary carcinomas of rats fed the 20%-fat diets was 2-10 times higher than in mammary fat pads of control rats.(ABSTRACT TRUNCATED AT 250 WORDS)

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1988

Computed tomography in the evaluation of lymphoma of the uterine cervix.

Primary involvement of the uterine cervix is a rare presentation of extranodal lymphoma. The clinical and computed tomography findings are described in four patients ranging from 23 to 74 years of age. All presented with vaginal bleeding. Computed tomography findings were similar to those of other primary pelvic neoplasms, with diffuse uterine enlargement and lobular contour alteration often mimicking fibroids. Lymphadenopathy was not observed in comparison to secondary lymphoma of the female genitalia. All patients had excisional biopsies. One patient had an initial TAH and BSO. Histology was varied with one case of large cell lymphoma, one of diffuse histiocytic, one of unclassifiable poorly differentiated lymphoma, and one of nodular poorly differentiated lymphocytic lymphoma that was finally classified as granulocytic sarcoma. Disease extent could be assessed by computed tomography and aided treatment planning. In conclusion, computed tomography was found to be useful in the evaluation of uterine lymphoma. Although the findings are not specific, the local tumor extent can be evaluated at the same time as other sites of potential involvement.

Adult↗
PubMed1988

Endocrine function following high dose proton therapy for tumors of the upper clivus.

The endocrine status of patients receiving proton radiation for tumors of the upper clivus was reviewed to evaluate the effect of high dose treatment on the pituitary gland. The fourteen patients had chordomas or low grade chondrosarcomas and were all treated by the same techniques. The median tumor dose was 69.7 Cobalt Gray Equivalent (CGE) with a range from 66.6 to 74.4 CGE. (CGE is used because modulated protons have an RBE of 1.1 compared to 60Co). The daily fraction size was 1.8-2.1 CGE. The median follow-up time is 48 months, ranging from 30 to 68 months. All treatments were planned using a computerized multi-dimensional system with the position of the pituitary outlined on the planning CT scan. Review of the dose distribution indicated that the dose to the pituitary ranged from 60.5 to 72.3 CGE, with a median of 67.6 CGE. One female patient had decreased thyroid and gonadotropin function at the time of diagnosis and has been on hormone replacement since that time. The other three females were all pre-menopausal at the time of radiotherapy. At this time four patients (3 males and 1 female) have developed endocrine abnormalities 14 to 45 months after irradiation. All four had evidence of hypothyroidism and two have also developed corticotropin deficiency. The three males had decreased testosterone levels; the female patient developed amenorrhea and hyperprolactinemia. All four are asymptomatic with ongoing hormone replacement.

Adolescent↗
PubMed1988

The role of MR and CT in evaluating clival chordomas and chondrosarcomas.

Sixteen chordomas and nine chondrosarcomas of the clivus were evaluated with CT and MR either before (22 cases) or after (three cases) treatment with proton beam irradiation. The ability of these imaging techniques to provide information necessary to direct patient treatment was studied. The tumor was detected and its gross margins were identified by both techniques in all instances. No reliable diagnostic features allowing differentiation between these two tumors were encountered. MR generally was superior in defining the exact position of the brainstem and optic chiasm relative to the tumor, and it frequently provided superior information about tumor extension into the nasopharynx and cavernous sinus. CT was always better than MR in demonstrating tumoral calcification and in defining the exact anatomy of bone destruction. MR was generally superior to CT in demonstrating the position of the cavernous internal carotid artery relative to the tumor and often provided superior visualization of the vertebral and basilar arteries. In cases in which bone-induced artifact obscured the interface between the neural axis and tumor in the CT image, or in which the tumor had suprasellar extension and was likely to compress the optic chiasm and tracts, MR was of great value in planning irradiation therapy. The high occurrence of clinically asymptomatic signal intensity alterations in the MR studies of previously treated patients appears to limit the differential diagnostic value of this information. Given its greater availability and lower cost, CT appears to be the technique of choice for routine follow-up of previously treated patients.

Adolescent↗
PubMed1988

The locations of collagens with different thermal stabilities in fibrils of bovine reticular dermis.

The techniques of differential scanning calorimetry and electron microscopy were combined to locate collagens with different thermal stabilities in bovine dermis. When calfskin was heated at 1.25 degrees C/min, denatured cores developed in the fibrils at 65 degrees C, leaving native-banded sheaths. Coincident with the initiation of shrinkage and loss of molecular orientation at 68 degrees C, the sheaths of the fibrils began to be denatured at distributed sites along the fibrils. At 80 degrees C the collagen lost its organized fibrillar structure. When thermally labile crosslinks had been stabilized by reduction with borohydride, an endotherm lying above 66 degrees C was suppressed, with proportional lowering of the total enthalpy change, and a fibrous texture revealing a helical subfibrillar structure remained. The three populations of collagen are located in the same fibrils. One, located in the cores of the fibrils, is half denatured at 68 degrees C. Another, established by crosslinks, is competent to sustain the regular appearance of fibrils even after 56% of the collagen in them has been denatured. This population is located as sheaths at the peripheries of the collagen fibrils. A third, denaturing below 59 degrees C, is codistributed with one or both of the two others.

Animals↗
PubMed1988

Intraoperative decisions based on angioscopy in peripheral vascular surgery.

We describe the technique of intraoperative angioscopy for delineation of peripheral vascular anatomy. Angioscopes with outer diameters of 0.85-2.9 mm have been used during 86 peripheral vascular procedures. Angioscopic inspections were performed during 68 femoral popliteal bypasses, four aortofemoral bypass grafts, one abdominal aortic aneurysm, two extra anatomic axillary femoral bypass grafts, and 11 other vascular procedures. We obtained useful images in 73 of 86 procedures (85%), thereby yielding 118 angioscopic inspections (53 arteries, 37 anastomoses, and 28 vein grafts). Changes in intraoperative management based on angioscopic findings included revision of five of 37 (14%) anastomoses, deletion of four of 31 (13%) completion angiograms, revision of eight of 17 (47%) in situ venous valves, and repetition of thrombectomy in six of seven (86%) cases. In 22 of 73 (30%) peripheral angioscopies, potential causes of graft occlusion were recognized. Complications from intraoperative angioscopy have included one anastomotic flap from intimal disruption that required anastomotic revision. Three small flaps, possibly resulting from angioscopic trauma, were recognized but appeared to have no clinical significance. In conclusion, intraoperative angioscopy provides visual assessment of luminal patency and anastomotic anatomy. This assessment alters intraoperative procedures in some cases and cannot be obtained by angiography.

Adult↗
PubMed1987

Studies on the molecular organization of rat insulin secretory granules.

Secretory granule-enriched fractions prepared from isolated rat islets of Langerhans, previously labeled in culture for 18 h with [3H]leucine, have been lysed and separated into pH 5.4 soluble and insoluble fractions by zonal sucrose gradient centrifugation. A high proportion of both labeled and immunoreactive rat insulins I and II were recovered in the insoluble granule core fraction in the expected ratio of approximately 60/40, respectively. Essentially equivalent amounts of the rat C-peptides on a molar basis were recovered in the granule supernatant fractions. The proportion of labeled proinsulin in the granule core fraction was less than 2% relative to insulin, while the soluble fraction contained about 8%, which probably arose mainly from disrupted proinsulin-rich noncrystalline prosecretory vesicles. Electron microscopic examination of the granule core fraction revealed large numbers of well preserved crystalline cores exhibiting typical dimensions and regular internal spacings of normal mature rat beta-granule inclusions. These results provide direct biochemical evidence that the beta-granules are nonuniform in composition with the insulin contained mainly in a crystalline state in the electron-dense central inclusions while the C-peptide is dissolved in the fluid bathing the crystalline hormone. The significance of this structural organization of the beta-granule is discussed.

Animals↗