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Biomedical subjects

S Brown

Publications and source records attributed to S Brown.

At least 469 records · Page 26Linked to original sources

Organizational planning: a program evaluation survey of AACE members.

The Long Range Planning Committee of the American Association for Cancer Education (AACE) has completed a comprehensive survey of AACE members. The survey was distributed in July and August 1989 to 592 AACE members, and 360 (61%) returned completed forms. The respondents did not differ markedly from the membership as a whole on selected member characteristics. Survey questions addressed the following aspects of the AACE: Annual Meeting, Special Interest Sections, Liaison Relationships, Journal of Cancer Education (JCE), and Communications. Results showed that the AACE is healthy and responsive to the needs of its members. Several areas needing attention were indicated, but no significant concerns were noted.

Communication↗

Interleukin-5 increases the expression of alkaline phosphatase activity in murine B lymphocytes.

Interleukin-5 (IL-5) was shown to enhance, in a dose-dependent fashion, the expression of alkaline phosphatase (APase) activity in splenic B cells stimulated with dextran sulphate (DXS). The potentiating effect of IL-5 was still more evident when assayed in large B cells than in small resting B cells, whereas IL-2, IL-4 and IL-6 were devoid of activity. Concomitant with increased APase expression, cell-cycle analysis by flow cytometry showed that large B cells in the early G1 phase were stimulated by IL-5, in conjunction with DXS, to enter G1B and to progress further through S and G2/M. A phosphorylation-dephosphorylation pathway could, thus, be involved in IL-5 transmembrane signalling.

Adenosine Triphosphatases↗

Evidence for a functional link between profilin and CAP in the yeast S. cerevisiae.

CAP is a component of the S. cerevisiae adenylyl cyclase complex. The N-terminal domain is required for cellular RAS responsiveness. Loss of the C-terminal domain is associated with morphological and nutritional defects. Here we report that cap- cells bud randomly and are defective in actin distribution. The morphological and nutritional defects associated with loss of the CAP C-terminal domain are suppressed by over-expression of PFY, the gene encoding profilin, an actin- and polyphosphoinositide-binding protein. The phenotype of cells lacking PFY resembles that of cells lacking the CAP C-terminal domain. Study of mutated yeast profilins and profilins from Acanthamoeba suggests that the ability of profilin to suppress cap- cells is dependent upon a property other than, or in addition to, its ability to bind actin. This property may be its ability to bind polyphosphoinositides. We propose that CAP and profilin provide a link between growth signals and remodeling of the cellular cytoskeleton.

Actins↗

AIDS research at NIH.

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Acquired Immunodeficiency Syndrome↗

Observations on the effect of chimeric anti-CD4 monoclonal antibody in patients with mycosis fungoides.

Chimeric (murine/human) anti-CD4 monoclonal antibody was infused into seven patients with mycosis fungoides. Successive patients received doses of 10, 20, 40, and 80 mg of antibody twice a week for 3 consecutive weeks. All patients had some clinical improvement, but responses were of relatively short duration. Serum levels of chimeric antibody varied as a function of dose. At the 80-mg dose level, antibody was readily observed in biopsied skin lesions. Although there was coating by antibody of most CD4 positive cells in the blood, there was no significant depletion of CD4 positive cells. Low-level antibody responses against the mouse Ig variable region and human Ig allotypic constant region determinants were observed in several patients, but none were of clinical significance. All but two patients made primary antibody and T-cell proliferative responses to a simultaneously administered foreign protein test antigen. However, there was marked suppression of the mixed lymphocyte reaction. We conclude that at the dose levels studied, a chimeric anti-CD4 monoclonal antibody (1) had some clinical efficacy against mycosis fungoides; (2) was well tolerated; (3) had a low level of immunogenicity; (4) had immediate immunosuppressive effects; and (5) did not induce tolerance to a co-injected antigen.

Adult↗

Developmental toxicity of pentostatin (2'-deoxycoformycin) in rats and rabbits.

The developmental toxicity of the potent adenosine deaminase (ADA) inhibitor, pentostatin (2'-deoxycoformycin), was investigated in pregnant rats and rabbits administered daily iv doses during organogenesis. Rats received 0, 0.01, 0.10, or 0.75 mg/kg on gestation days 6-15 and rabbits received 0, 0.005, 0.01, or 0.02 mg/kg on gestation days 6-18 and maternal and fetal parameters were evaluated on gestation day 21 (rats) or 30 (rabbits). Live fetuses were examined for external, visceral, and skeletal malformations and variations. In rats, maternal body weight gain and food consumption were significantly suppressed at doses of 0.10 and 0.75 mg/kg during the treatment period but returned to control levels during posttreatment. Increased postimplantation loss and decreased numbers of live fetuses, litter size, and fetal body weight were observed at 0.75 mg/kg. A statistically significant increase in the incidence of vertebral malformations occurred at 0.75 mg/kg. The incidence of certain skeletal variations (extra presacral vertebrae, extra ribs, hypoplastic vertebrae) was also increased at 0.75 mg/kg. Ossification of cervical centra was reduced at 0.75 mg/kg compared with controls. In rabbits, marked maternal toxicity (death, body weight loss, and decreased food consumption) and reproductive toxicity (abortion and premature delivery) occurred in all pentostatin-treated groups. However, there were no significant effects on number of live fetuses, pre- or postimplantation loss, litter size, or fetal body weights in the animals with live litters. There was also no apparent increase in the incidence of malformations or variations in the live fetuses of pentostatin-treated rabbits. Thus, these studies demonstrate developmental toxicity of pentostatin in rats and rabbits, and teratogenicity in rats, at maternally toxic doses.

Abnormalities, Drug-Induced↗

Follicular lymphoma: a model of lymphoid tumor progression in man.

Human follicular lymphoma can be viewed as a malignancy in evolution. Since this disease is composed of a clonal population of B lymphocytes all expressing a given immunoglobulin light chain and heavy chain, it seems possible that the initial transforming event, the t(14; 18) chromosomal translocation, occurs in a cell already committed to the expression of a particular VH and VL gene. A panel of antibodies has been assembled which define a set of idiotypes expressed repeatedly by B-cell lymphomas. Nonetheless, VH gene usage in follicular lymphoma tumors appears to reflect the normal B-cell repertoire. Growth of follicular lymphoma appears to be partially under normal regulatory control. The expanding malignant B-cell clone grows in follicles with particular apposition to follicular dendritic cells and heavy infiltration with CD4+ T cells. Interaction with T cells can induce the proliferation of follicular lymphoma cells. This tumor eventually evolves into a diffuse large-cell lymphoma which is highly aggressive and lethal. It is now clear that the malignant progression occurs from a single cell within the expanding follicular lymphoma clone. A panel of monoclonal antibodies to cell surface molecules has been generated that inhibit proliferation of diffuse lymphoma cell lines, and some of the target molecules have been partially characterized. Therapeutic application of anti-idiotype monoclonal antibodies has shown a high degree of tumor responsiveness, but ultimately escape of idiotype-negative variant cells occurs. These variants arise as a result of extensive somatic point mutation in the VH and VL genes of follicular lymphoma. Active immunization can result in an immune response by patients directed against the idiotype expressed on their own B-cell tumors.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Communication↗

Histological changes following submucosal Teflon injection in the bladder.

Histological examination following subureteric Teflon injection was carried out on 32 ureters and four granulomatous polyps. When the Teflon was correctly placed in the submucosa it remained circumscribed and reflux was more likely to be corrected. If the Teflon was placed more deeply it became diffuse, caused a giant cell reaction, and was less likely to correct the reflux. The granulomatous polyps may represent a reaction to leakage of Teflon from the injection site.

Foreign-Body Reaction↗

Reversal of degenerative changes in the scrotal testis after orchidopexy in experimental unilateral cryptorchidism.

Unilateral cryptorchidism was induced in newborn Wistar rat pups. Using DNA flow cytometry to compare scrotal testes of control and cryptorchid animals, there was a significant difference decrease in the haploid cell population in cryptorchid animals from 40 days of age. Orchidopexy was performed at 30 days (at the time of normal descent), 50 days (pubertal), and 90 days (fully mature adult). When with sham-operated control and cryptorchid animals of the same age were compared, there was no decrease in the haploid population at any age in the scrotal testis if orchidopexy was performed at 30 days; the degenerative changes could be reversed to normal if orchidopexy was performed at 50 days; however, if operation was delayed to 90 days, the decreased numbers of haploid cells in the scrotal testis were neither prevented nor reversed and remained significantly lower than normal controls (P less than .005). This study shows that orchidopexy performed before adulthood reverses secondary degenerative changes in the scrotal testis in an animal model of unilateral cryptorchidism.

Age Factors↗