Improved survival among patients treated with adjuvant tamoxifen after mastectomy for early breast cancer.
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Biomedical subjects
Publications and source records attributed to A Wilson.
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The innervation of the chicken ovary was investigated with special emphasis on adrenergic nerves in the follicular wall. Quantitative determinations of catecholamines (CA) by high-performance liquid chromatography and electrochemical detection (hplc-ed) revealed 15.4 +/- 3.3 ng/mg protein of norepinephrine (NE) and 3.14 ng/mg protein of epinephrine (E), with even larger amounts in the cranial part of the ovary close to the adrenal gland. Serial sections that had been processed for the visualisation of aminergic nerves (Falck-Hillarp- or glyoxylic acid techniques) showed CA localized in nerve-fibre bundles; cell bodies of chromaffin and sympathetic neurons were only found at the ovarian-adrenal junction suggesting that ovarian nerves stored considerable quantities of E. An antiserum against bovine phenylethanolamine N-methyltransferase (PNMT, the E-synthesizing enzyme) produced no immunostaining in chicken ovary or adrenal gland, due to a lack of cross-reactivity between the antiserum and chicken PNMT. Serial sections processed alternately for the visualisation of aminergic nerves and myosin (from chicken gizzard) immunoreactivity revealed a scarce nerve supply of contractile cells in the theca externa compared to an extraordinarily dense innervation of the endocrine interstitial tissue of the theca interna. This distribution pattern of nerve fibres in the follicular wall was confirmed by electron microscopy in ovarian tissue that had been pretreated with 5- or 6-hydroxydopamine (HDA). More than 90% of the terminal axons were specifically labeled by these false adrenergic transmitters. Many of these terminals were seen in close contact (20 nm) with steroidogenic cells suggesting a neuromodulatory function of CA in hormone synthesis and/or release. It is yet unclear whether E and NE are stored in separate or identical axon moieties and within the same organelles. Choline acetyltransferase activity, which was taken as a measure for a cholinergic nerve component in the ovary, amounted to only 7% of its adrenal activity. It is suggested that the chicken ovary may serve as an excellent model to investigate the modulatory role of nerves in the endocrine function of the ovary.
T cells cultured at limit dilution for 8 days in a concanavalin A-stimulated, filler-cell and growth factor-supported system produced cytolytic clones with high efficiency. These clones were not specific, lysing a wide range of targets, syngeneic and allogeneic, of tumor and normal cell origin. Lysis was a cell-mediated phenomenon but was not blocked by anti-Ly-2. One H-2-negative target was lysed, but one was resistant. Xenogeneic (human) tumor cells were not lysed. The cells in the clones were large, vacuolated, granular lymphocytes. They originated from single Ly-2+ responder cells and not from irradiated filler cells. Therefore, activated lymphocyte killers and other natural killer-like cells may be differentiated elements of the Ly-2+ T-cell lineage.
This paper describes the development of multidimensional measures of nursing-home patients' functioning. The technique was designed to gather information directly from the patients, using demonstrated ability in place of self-report wherever possible. Six domains are tapped: physiologic, activities of daily living, affective, cognitive, social, and satisfaction. Test-retest reliability ranges from .59 for social interaction to .85 for affect. Validity was tested by replication on successive waves of data as well as discriminant and content validity.
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An 18-year-old male student had a 3-month history of partial seizures with cognitive symptomatology, with occasional secondary generalization. After 3 weeks of treatment with clobazam 20 mg a day, the patient developed, in association with his seizures, a neologistic jargon dysphasia but with loss of inflection, volume, and rhythm of speech, presumably as a result of the effect of the clobazam.
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The effect of 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid 3-[2-(N-benzyl-N-methyl amino)] ethyl ester 5-methyl ester hydrochloride (nicardipine, RS-69216, YC-93), on the healing of myocardial infarcts has been examined in dogs surviving for 3 months after ligation of the left anterior descending coronary artery (LAD). Three groups of 12-14 dogs were subjected to the following treatments: a) Group X received one-month oral pretreatment (1-2 mg/kg/d) with post-ligation i.v. treatment delayed for 1 h (10 micrograms/kg followed by 2 micrograms/kg/15 min for 5 h) and oral treatment (1-2 mg/kg/d) for 3 months (n = 9 survivors). b) Group Y received oral placebo for one month, i.v. saline vehicle every 15 min for 5 h commencing 1 h postligation, and oral placebo for 3 months (n = 8 survivors). c) Group Z received oral placebo for one month as in group Y, i.v. and oral drug treatment post-ligation as for group X (n = 10 survivors). Recordings were made of general haemodynamics and at post mortem, each heart was X-rayed and sliced transversely to give 14 sections from which detailed observations were made on left ventricular (LV) geometry. Comparative morphological measurements were available from filed data for 11 normal dog hearts (designated group C) of similar type. Nicardipine treatment significantly modified the general haemodynamic responses to LAD ligation particularly in maintaining a low LV systolic pressure and inhibiting elevation of LV end diastolic pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
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A limit-dilution microculture system is presented in which almost all mature T cells, cultured at a level of about 1 cell/well, grow and expand to clones averaging 60,000 cells over an 8-9 day period. Cloning efficiency is 70-100%, so the set of the expanded clones is representative of the starting T-cell population. T cells of all Lyt phenotypes form clones of progeny cells. The system involves culture in flat-bottom microtitre trays, in the presence of concanavalin A as the initiating stimulus, together with appropriately irradiated spleen filler cells and a supplementary source of soluble T cell growth factors. The resultant clones may be screened for cytolytic function, as described in the accompanying paper. The system may be used to assay the level of T cells capable of expansion or precursor function (PTL-p) by using [3H]TdR uptake as a readout for the presence or absence of proliferating clones. Analysis of the frequency of positive cultures shows a good fit to the expected Poisson distribution, with no evidence of complicating suppressor or helper effects.
Complete papillary necrosis in rats can be induced within 1 month following a single injection of 2-bromoethylamine hydrobromide (BEA) (50 mg, i.v.). Utilizing a combination of clearance and balance techniques the effects of complete absence of the papilla was examined as regards urinary acidification, whole kidney glomerular filtration rate (GFR), single nephron GFR, and morphology. Whole kidney GFR was not different from control, however, the percent filtering juxtamedullary nephrons was markedly diminished (87.2 +/- 2.1 vs. 31.5 +/- 3.6% filtering, control vs. BEA, respectively, P less than 0.001) and significantly reduced in the superficial nephrons (80.6 +/- 3.6 vs. 62.2 +/- 6.1% filtering, control vs. BEA, respectively, P less than 0.05). There was a significant decrease in juxtamedullary single nephron GFR and an increase in the superficial single nephron GFR as assessed by the quantitative Hanssen's technique in the animals with chronic papillary necrosis. Complete papillary necrosis was associated with normal arterial bicarbonate concentration, pH, and plasma electrolyte concentrations. At the same degree of acidemia (induced by NH4Cl administration) minimal urinary pH, ammonium excretion, and titratable acid excretion were not different than seen in age matched controls. The response to Na2SO4 infusion and phosphate infusion was the same in both groups of animals. The urine-blood (U-B)pCO2, and index of urinary acidification, was identical in BEA and control animals. Scanning electron microscopy showed scarring of the juxtamedullary glomeruli one month after BEA. The papilla was sloughed and lying free in the renal pelvis in every experimental animal. These data demonstrate that complete papillary necrosis is not associated with acidosis nor a defect in urinary acidification.
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The intermediate or "pre-progenitor" B-cell subpopulation giving primary adoptive responses has been found by this laboratory to be s-IgD-, whereas other laboratories have reported the progenitors of primary adoptive responses to be s-IgD+. This difference appears to depend on the recent history of environmental stimuli received by the mice. Deliberate administration of a complex non-specific stimulus, designed to mimic the effects of infection or certain types of experimental manipulation, shifted "pre-progenitor" activity from the s-IgD- compartment to the s-IgD+ compartment within 24 h. Neither horse erythrocytes (HRC) nor lipopolysaccharide (LPS) alone produced a reproducible effect, but the combination of HRC with low doses of LPS produced a marked shift to s-IgD+ activity. Some earlier experiments from this laboratory suggesting a striking effect with HRC alone probably resulted from suspension of HRC in saline contaminated by LPS-like material. Priming with HRC alone, under conditions which did not induce s-IgD, nevertheless stimulated the "pre-progenitors" to enter cell cycle. Three conclusions are drawn: (1) The stimulus for induction of s-IgD is not identical with the non-specific stimulus which selectively induces cell division in this intermediate B-cell subset; (2) the presence of IgD on the surface per se does not prevent the non-specific activation of these cells into division; (3) the absence of s-IgD is only a useful marker of the "pre-progenitor" subset if the mice are maintained under specific pathogen-free conditions and exogenous stimuli are controlled.
Evidence is presented that a dividing, Thy 1 . 2 positive and NK 1 . 2 positive cell with a suppressive effect on adoptive responses is present in the spleens of normal and athymic mice, and that its function may be enhanced by non-specific antigenic stimulation. NK cells may thus exert a controlling function on the proliferation and differentiation of B cells. The main experimental observation is that under certain assay conditions incubation of spleen cells with 3H-TdR in order to kill dividing, non-specifically activated 'pre-progenitor' B cells may actually give a marked increase rather than a decrease in a subsequent hapten-specific primary adoptive response. An activated 'suppressor' population was proposed as the reason for this effect. This anomalous effect may be avoided and the cycle state of the B cells assessed by prior elimination of cells bearing Thy 1 antigen, together with the use of a more reliable hydroxyurea incubation to kill dividing B cells.
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