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Biomedical subjects

S Cooper

Publications and source records attributed to S Cooper.

At least 325 records · Page 18Linked to original sources

Effect of an osmotic gradient on antidiuretic hormone-induced endocytosis and hydroosmosis in the toad urinary bladder.

The luminal (apical) border of the epithelium of the bladder in the well-hydrated toad is relatively impermeable, so the bladder usually stores hyposmotic urine. When antidiuretic hormone (ADH) increases apical membrane osmotic permeability dramatically, water is resorbed from hyposmotic mucosal solution; in the presence of hyposmotic or isosmotic mucosal solutions, ADH concomitantly induces exocytosis at the apical border of granule-rich (G) cells. Then ADH induces endocytosis at this border. We describe how an osmotic gradient affects ADH-induced endocytosis and hydroosmosis in vitro. We can assess ADH-induced endocytosis in gradient and no-gradient bladders by applying a double-marker technique that distinguishes among endocytosis, completed internalization of previously surface-attached membrane, and surface invagination by comparing the number of horseradish peroxidase (HRP) uptake bodies (endocytosis) with the number of ruthenium red (RR)-delineated bodies (surface invaginations). With this approach we find that gradient bladders have approximately six times more ADH-induced endocytosis than no-gradient bladders during 45-60 min of ADH stimulation. Furthermore, at 60 min approximately 50% of the HRP-containing structures in no-gradient bladders remain surface connected compared with approximately 1% in gradient bladders. In parallel physiological studies, no-gradient bladders reach and maintain higher induced osmotic permeabilities than gradient bladders. These findings support the hypothesis that endocytosis plays an active role in reestablishing impermeable apical surface characteristics in toad bladder.

Animals↗

Elective cardiac operation in a patient with severe hemophilia and acquired factor VIII antibodies.

This paper describes a successful cardiac operation in a young boy with hemophilia, congenital heart disease, severe factor VIII deficiency, and an acquired high titer antibody to factor VIII. To our knowledge, there have been no published cases of elective cardiac operations in a person with severe hemophilia and an accompanying complex problem. Utilizing the team approach, we administered a megadose bolus of factor VIII concentrate preoperatively (eight times the calculated dose), followed by a continuous intravenous infusion at 500 units/hr throughout the procedure and at a reduced dose for the first 5 postoperative days. With the anamnestic rise in factor VIII antibody on day 5, activated prothrombin complex concentrates were substituted for factor VIII and provided continued adequate hemostasis during the remaining 9 postoperative days. The rapid infusion of large quantities of factor VIII was effective in neutralizing the low titer inhibitor and providing normal hemostasis during the procedure. In addition, activated prothrombin complex concentrates were substituted for factor VIII coagulant without recurrent bleeding or thromboembolic phenomena.

Antibodies↗

Functional activities of acidic isoferritins and lactoferrin in vitro and in vivo.

The functional activities of acidic isoferritins (AIF) and lactoferin (LF) were evaluated. The inhibitory activity of AIF (AIFIA) was inactivated by preincubation with a monoclonal antibody (2A4) against AIF, but AIFIA was not inactivated by another monoclonal antibody against AIF (1C5), by a monoclonal antibody (3A5) against basic isoferritins, or by a heteroantiserum (LFT) against basic isoferritins. Monoclonal 2A4 also inactivated the inhibitory activity against colony formation by granulocyte-macrophage (CFU-GM) progenitor cells that was constitutively released by human monocytes or induced by human monocytes in the presence of OKT4+ lymphocytes. In addition to OKT4+ lymphocytes, the release of AIFIA from human monocytes was modulated by iron-saturated human LF and OKT8+ lymphocytes, both of which suppressed the release of AIFIA. Evidence for the physiologic relevance of AIF as a regulator of myelopoiesis was presented, in that human AIF suppressed the numbers of CFU-GM, BFU-E, and CFU-GEMM per femur and the cycling status of these cells in mice recovering from a sublethal dosage of Cytoxan. Abnormalities in LF and AIF interactions were found with cells from a pediatric patient with neutrophilia of unknown etiology that were consistent with the disease manifestations of neutrophilia. Polymorphonuclear neutrophils (PMN) from the patient contained low levels (1%-10% of control) of immunologically reactive LF and the LF found was ineffective as a suppressor molecule for the release of GM-CSF from normal mononuclear blood cells. In addition, the patient's GM-CSF releasing mononuclear blood cells were insensitive to the suppressive effects of purified LF, and colony formation by the patient's CFU-GM, but not BFU-E or CFU-GEMM, were insensitive to the suppressive effects of purified AIF. When the activity of purified AIF was assessed against mouse bone marrow cells under serum-free conditions, it was apparent that serum was not needed for the suppressive activity of AIF and that in some cases, serum actually masked the effects of AIF. Human monoblast cell line U937 was found to be a good model in vitro for the actions of LF and AIF; U937 cells induced for Ia-antigens by human gamma interferon were separated into populations of Ia-antigen+ and Ia-antigen- cells by fluorescence activated cell sorting (FACS), and LF and AIF suppressed colony formation only by the Ia-antigen+ U937 cells. A comparative analysis of bovine and human LF against release of GM-CSF from human mononuclear cells demonstrated that both were active in their iron-saturated form.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Classical conditioning, decay and extinction of cocaine-induced hyperactivity and stereotypy.

Following 10 daily pairings of multiple conditioned stimuli with injection of cocaine (15 mg/kg), the presentation of the stimuli alone elicited behaviors in rats similar to those induced by cocaine. The behaviors included increased duration or frequency of rearing, sniffing, head bobbing, and horizontal locomotor activity (crossing). The level of the conditioned response for several of these behaviors approximated that induced by the drug itself. The conditioned drug effect showed decay over 15 days but little extinction during 4 daily trials. Brain concentrations of the dopamine metabolites, homovanillic acid and dihydroxyphenylacetic acid, were similar in the conditioned and pseudoconditioned control groups in both the caudate and mesolimbic areas. The behavioral results demonstrate that, in a classical conditioning paradigm, previously neutral stimuli can elicit behaviors similar to those induced by cocaine and that certain conditioned responses show time related decline. This agrees with the reported conditioning of amphetamine's behavioral effects but differs in terms of the action on brain dopamine turnover.

3,4-Dihydroxyphenylacetic Acid↗

A critique of the use of DNA synthesis as a measure of the effect of mitogens on lymphocytes.

The use of DNA synthesis as a measure of mitogenic activity in lymphocytes is reanalyzed in the light of the Continuum Model, and it is suggested that although lymphocytes may have a linear response with regard to mitogen concentration, the curves using thymidine may show a threshold response at low concentrations and a decrease in activity at high concentrations.

Cell Division↗

Second malignant neoplasms in patients treated for Hodgkin's disease with radiotherapy or radiotherapy and chemotherapy.

The incidence of second malignant neoplasms (SMN) was assessed in 248 patient with Hodgkin's disease (HD) treated by radiotherapy alone (XRT) or in combination with chemotherapy (XRT + C) between January/1960 and June/1977. Radiation therapy was categorized as less than extended field (less than EF), extended field (EF) or total nodal irradiation (TNI). Chemotherapy was scored as single agent (SAC) or multiagent (MAC). MAC consisted primarily of either nitrogen mustard, vincristine, prednisone and procarbazine (MOPP) or cyclophosphamide, vinblastine, procarbazine and prednisone (CVPP). Ten metachronous malignancies occurred 1-21 years (median 10 years) after the diagnosis of HD. With a median follow-up of 6 years the observed-to-expected ratio (O/E) was 4.2 for XRT alone and 7.6 for XRT + MAC. For 46 patients with greater than or equal to 10 years follow-up (median 13 years) the O/E ratio was 16.1 for XRT and 26.5 for XRT + MAC. All SMN occurred in patients who had not had a splenectomy at or prior to the time of HD diagnosis. Only four of nine solid SMN were within treatment portals or near portal margins. The diagnosis of another malignant neoplasm was made prior to or simultaneous with the diagnosis of HD in four additional patients. This observation, and the occurrence of five of six SMN outside of the treatment field in the XRT alone group, suggest that there may be factor(s) associated with the incidence of SMN in HD in addition to treatment itself.

Adolescent↗

The central dogma of cell biology.

The Continuum Model proposes that preparations for DNA synthesis occur continuously during all phases of the division cycle. Various stimuli activate cell proliferation by changing the rate of initiator (protein) synthesis. Cell division does not initiate any process regulating cell proliferation. Cell division is the end of a process and the beginning of nothing. The alternative model which has cell proliferation regulated in the G1 phase of the division cycle is reexamined and the two types of evidence for this model, G1-variability and G1-arrest are shown to be compatible with the Continuum Model. Here, the Continuum Model is generalized to produce a new look at the logic of the division cycle in prokaryotes and eukaryotes. This new view, the Central Dogma of Cell Biology, is presented and two predictions are made. I propose that (i) cell division does not have any regulatory function, and (ii) that DNA synthesis may, indeed, have some affect on the synthesis of initiator.

Cell Division↗

Identification and characterization of the adenosine 3',5'-cyclic monophosphate binding proteins appearing during the development of Dictyostelium discoideum.

A photosensitive, radioactive analogue of cyclic adenosine monophosphate, 8-azido-adenosine 3',5'-[32P]monophosphate (8-N3-cyclic AMP), was used to label the cyclic AMP binding proteins of Dictyostelium discoideum. During development cytosolic proteins appear which are specifically labeled by the photoaffinity agent. The proteins are developmentally regulated since they are only found in starved, developing cells. Unlabeled cyclic AMP competes specifically with the labeled analogue for protein binding sites in contrast to unlabeled 5'-AMP which does not compete. A mutant which develops spores but is deficient in stalk cell production produces a different set of cyclic AMP binding proteins from the parent strain.

Affinity Labels↗

Medical students' attitudes toward cancer.

The purpose of this study was to determine whether or not attitudes of medical students toward the cancer patient are as negative as their attitudes toward the chronically ill patient. A questionnaire designed to measure student attitudes toward cancer was administered to 122 medical students. Two versions of the questionnaire were developed. One version referred specifically to attitudes toward cancer patients while the second version assessed attitudes toward patients in general. Significant differences were found between student attitudes toward cancer patients and patients in general. Support was found for the existence of negative attitudes in the treatment of cancer patients. Implications of these findings and teaching modifications are discussed.

Attitude↗

A unifying model for the G1 period in prokaryotes and eukaryotes.

A model to explain the cell division cycle in both prokaryotes and eukaryotes is presented. No specific 'G1 functions' take place during the G1 period, which is merely part of a larger period for the preparation of DNA synthesis which began at the previous initiation of DNA synthesis. A G1 period exists merely because the doubling time of the cells is greater than the sum of the S and G2 periods.

Bacteria↗

Gas chromatographic determination of amitriptyline, nortriptyline and perphenazine in plasma of schizophrenic patients after administration of the combination of amitriptyline with perphenazine.

A specific and sensitive gas-chromatographic technique using a common extraction procedure for the quantitative determination of amitriptyline, endogenous nortriptyline and perphenazine in plasma of schizophrenic patients receiving therapeutic doses of a combination of amitriptyline and perphenazine (Etrafon) has been developed. The lower limits of detection are 20 ng/ml for amitriptyline, 1 ng/ml for nortriptyline and 5 ng/ml for perphenazine. Amitriptyline is estimated with a flame ionization detector. Nortriptyline is quantitated using an electron capture detector after converting it to its heptafluorobutyryl derivative by reaction with the appropriate anhydride. Perphenazine is also determined using an electron capture detector after forming its stable, trimethylsilyl derivative by reaction with N,O-bis-(trimethylsilyl)-acetamide. In individual patients, the steady-state plasma levels ranged from 44 to 215 ng/ml for amitriptyline, from 49 to 270 ng/ml for nortriptyline and from less than 5 to 20 ng/ml for perphenazine. Steady-state plasma levels data on amitriptyline, nortriptyline and perphenazine in 23 patients treated with Etrafon are presented.

Adult↗