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Biomedical subjects

B Hamilton

Publications and source records attributed to B Hamilton.

At least 109 records · Page 6Linked to original sources
PubMed1982

Generation of cytolytic T lymphocytes in thymectomized, irradiated, and bone marrow-reconstituted mice.

A model system has been developed to study extrathymic T cell differentiation. Mice have been thymectomized, lethally irradiated, and reconstituted with bone marrow cells depleted of Thy-1-positive cells. After 8 wk, the spleen cells of these 5athymic, bone marrow-reconstituted chimeras contain Thy-1-positive pre-cytolytic T lymphocytes (CTL) that are able to respond to antigen only when exogenous interleukin 2 is added to culture.. The phenotype of these pre-CTL is similar to that of thymocytes, suggesting that they may be an immature T cell. Initial evaluation of the CTL repertoire of these athymic mice demonstrates that the CTL generated to trinitrophenyl-modified syngeneic cells are H-2 restricted and that the CTL generated to alloantigens have many of the cross-reactivities observed in normal but not in nude mice. The discrepancies observed in the CTL repertoire between these thymectomized chimeras and nude mice are discussed.

Animals↗
PubMed1982

Pindolol: effects on blood pressure and plasma renin activity.

The influence of pindolol, other antihypertensive agents, or placebo upon plasma renin activity (PRA) was examined in five separate studies involving 249 subjects (pindolol), n = 149; propranolol, n = 43; methyldopa, n = 13; chlorthalidone, n = 16; placebo, n = 28). In addition, the subjects were stratified in for studies into low (n = 104), medium (n = 96), or high (n = 15) PRA categories according to baseline PRA and sodium excretion measurements. The response to antihypertensive therapy was analyzed in each PRA category. Pindolol and propranolol lowered PRA comparably at equivalent dosages, although this effect was not consistently observed in all studies or at all dosage levels. Methyldopa therapy was not associated with a decline in PRA and chlorthalidone elevated PRA. Pindolol and propranolol lowered both supine and erect diastolic blood pressure (BP) comparably. This effect was similar in subjects categorized as having low or medium PRA. Too few patients were studied with high PRA to derive statistically meaningful data. Pindolol lowered standing systolic BP to a greater extent than did propranolol, especially in the medium PRA category. It was concluded that pindolol, like other beta-adrenergic blockers, lowers PRA, that the effect of pindolol on diastolic BP is independent of the baseline PRA category, and that pindolol is more effective than propranolol in lowering standing systolic BP, at least in the medium PRA category.

Adult↗
PubMed1982

Long-term intermittent catheterization in the spinal cord injury patient.

Intermittent catheterization was used as a means of long-term bladder management in 85 patients with spinal cord injury. Of these patients followup data revealed that 28 (33 per cent) had reflux and/or hydronephrosis. Treatment in 15 patients consisted of increasing the frequency of catheterization to every 4 hours and avoiding high fluid intake during a relative short interval. Sphincterotomy was done in 3 patients, while 10 were placed on an indwelling catheter because of an inability to adapt to or refusal of other forms of treatment. The upper urinary tract changes noted seemed to be related to increased intravesical pressure, either from too long an interval between catheterizations or from marked detrusor hyperreflexia with sphincter obstruction. Close followup seems necessary in these patients.

Adult↗
PubMed1982

Translational control of catalase synthesis by hemin in the yeast Saccharomyces cerevisiae.

mRNA-dependent cell-free protein synthesis systems were prepared from a heme-deficient ole3 mutant of the yeast Saccharomyces cerevisiae grown either in the absence or in the presence of the heme precursor delta-aminolevulinate. When supplemented with total yeast mRNA, the two systems-from heme-deficient and from heme-containing cells-translate most mRNAs with comparable efficiencies. mRNAs coding for the hemoproteins catalase T and catalase A, however, are translated at a low rate by the system from heme-deficient cells whereas their translation in the system from heme-containing cells is comparable to that observed in a heterologous in vitro system from wheat germ. Addition of 10 muM hemin to the system from heme-deficient cells stimulates translation of catalase mRNAs significantly. Control experiments showed that the results obtained cannot be explained by specific proteinase or nuclease action. Together with previous findings indicating lack of translation of catalase T mRNA in heme-deficient cells in vivo, the results demonstrate that specific control of yeast catalase formation occurs at the level of translation.

Catalase↗
PubMed1982

Preparation of a mRNA-dependent cell-free translation system from whole cells of Saccharomyces cerevisiae.

A cell-free protein-synthesizing system has been prepared from Saccharomyces cerevisiae by mechanical breakage of cells, isolation of a 30000 x g supernatant fraction and removal of endogenous mRNA by treatment with micrococcal nuclease. The system thus isolated is dependent on added mRNA and translates yeast mRNA to discrete products, many of then identical with yeast proteins synthesized in vivo. Activity and properties of this system are comparable to those of other eukaryotic cell-free translation systems. It offers the following advantages, compared to yeast translation systems described previously. (a) Its isolation is simple and fast. (b) Since it is not isolated from spheroplasts there is no danger of its inactivation by contaminants in enzymes used for spheroplast preparation. (c) Isolation appears to be less strain-dependent and can be carried out starting from cells in various physiological states.

Cell-Free System↗
PubMed1982

Regulation of synthesis of catalases and iso-1-cytochrome c in Saccharomyces cerevisiae by glucose, oxygen and heme.

The regulation of the hemoproteins catalase T, catalase A and iso-1-cytochrome c was studied in the yeast Saccharomyces cerevisiae. Levels of catalase T and catalase A mRNAs are low or undetectable in anaerobic and heme-deficient cells, and in wild type strains grown on high glucose concentrations. Regulatory mutants (cgr4 and cas1), which have previously been shown to have high catalase T activity when grown in the absence of oxygen or on high glucose concentrations, have high levels of catalase T mRNA when grown under glucose repression conditions. Whereas no catalase T mRNA could be detected in a heme-deficient (ole3) single mutant, double mutants (ole3 cgr4) and (ole3 cas1) contain mature catalase T mRNA. Catalase T and A mRNAs are accumulated rapidly during adaptation of anaerobic cells to oxygen. Anaerobic and heme-deficient cells lack or have extremely low levels of iso-1-cytochrome c mRNA, which, like catalase mRNAs, is accumulated rapidly during oxygen adaptation. The results obtained demonstrate that glucose, oxygen and heme regulate the synthesis of the hemoproteins studied by controlling mRNA levels. In addition, posttranscriptional, probably translational control has to be postulated at least in the case of catalases, to explain the results obtained.

Catalase↗
PubMed1981

The anovulatory hamster: a comparison of the effects of short photoperiod and daily melatonin injections on the induction and termination of ovarian acyclicity.

Cyclic female hamsters were rendered anovulatory by daily subcutaneous melatonin injections (25 microgram/0.1 ml oil) in 29 days or by transfer to a short light cycle, LD 6:18 (lights 1000-1600 hrs) in 33 days. Estrous cyclicity was reinitiated in these animals in 44 or 45 days following cessation of melatonin injections or transfer to long light cycles (LD 14:10, lights 0600-2000 hrs), respectively. Exposure of both groups to LD 6:18 after reinitiation of estrous cyclicity caused a second cessation of ovulation in 75 (melatonin group) or 61 (short light cycle group) days. Thus, although both treatments disrupted estrous cyclicity for nearly 6 weeks, this was not sufficient to induce photorefractoriness (failure to respond to short light cycles with continued estrous cyclicity). Rather, every animal responded to LD 6:18 and ceased ovulating. Melatonin-induced anovulatory hamsters showed daily gonadotropin release patterns identical to those reported in hamsters in other anovulatory states (lactating, prepubertal, and photoinduced anovulatory hamsters); that is, peak LH and FSH release at 1700 hrs daily.

Animals↗
PubMed1981

Antagonism between epidermal growth factor and phorbol ester tumor promoters in human breast cancer cells.

It has been suggested that the phorbol ester tumor promoters act via the receptor-effector system for epidermal growth factor (EGF), since they interact with the EGF receptor system and mimic many of the effects of EGF in cultured cells. We have studied the interaction of phorbol esters with the EGF-responsive MCF-7 human breast cancer cell line. Similar to other systems, phorbol esters inhibit EGF binding in MCF-7 cells in a manner paralleling their potency as tumor promoters in mice. The effect is specific for EGF since the membrane binding of insulin is unaffected. Like EGF, the potent phorbol ester 12-O-tetradecanoyl-13-phorbol acetate (TPA) stimulates protein synthesis as indicated by a twofold increase in [(3)H]leucine incorporation into protein after 24 h in TPA. Cell morphology, however, is significantly different with TPA treatment. After 24-48 h in TPA, cells become markedly enlarged with increased cytoplasmic vacuolization and increased membrane microvilli. This is reflected in a fourfold increase in the protein/DNA ratio (control 13.1; TPA 55.9). Furthermore, TPA inhibits cell division in media with or without serum, and prevents growth stimulation by EGF. Low TPA concentrations (1.0 ng/ml) are active, and 10 ng/ml results in maximal inhibition of cell replication. Other phorbol esters inhibit MCF-7 cells relative to their tumor promoting activity in vivo and their ability to inhibit EGF binding in these cells. After 24 h in TPA, incorporation of [(3)H]thymidine into DNA is markedly reduced and the thymidine labeling index falls (33% to 2%) indicating very few S-phase cells. Growth inhibition is reversible by removing TPA from the medium. Similar inhibitory effects are seen with the two other human breast cancer cell lines studied, ZR75-1 and MDA-MB-231. In conclusion, phorbol esters may interact with the EGF receptor domain in MCF-7 human breast cancer cells, but they have distinct effects on cell morphology and growth suggesting alternative pathways of action. The antineoplastic activity of these compounds needs further investigation.

Breast Neoplasms↗
PubMed1980

Clonidine after renal ischemia to lessen acute renal failure and microvascular damage.

Clonidine, an antihypertensive drug that inhibits renin release and causes a water diuresis in normal animals, was tested for its ability to reduce the severity of post-ischemic acute renal failure produced in rabbits by clamping the left renal pedicle for 1 hour and removing the opposite kidney. Clonidine significantly lessened renal failure when given during, or 1 hours after, the ischemic insult in dehydrated rabbits. It was also effective when given during the ischemic insult in vasopressin-treated water-drinking rabbits but not in control water-drinking rabbits. In vasopressin-treated rabbits, clonidine lessened renal failure observed 2 days after the ischemic insult despite the fact that in the immediate postischemic period it lowered total renal blood flow, produced hypotension, and did not bring about lower plasma renin levels. Clonidine treatment resulted in less outer medullary microvascular damage (demonstrated by colloidal carbon staining), higher outer medullary blood flow 1 to 2 hours after unclamping, fewer casts, and higher creatinine clearance and free water clearance/creatinine clearance 4 to 6 hours after unclamping compared with controls. The effect of clonidine was unrelated to plasma renin activity. Clonidine did not alter plasma vasopressin concentration. Demeclocycline and lithium, two agents that blunt renal responsiveness to vasopressin, had a beneficial effect in dehydrated animals similar to that of clonidine, but the angiotensin II antagonist saralasin and the angiotensin converting enzyme inhibitor SQ20881 did not. Normal rabbits given a large dose of vasopressin in oil plus clonidine had significantly greater urine output and free water clearance and lower urine osmolality than did rabbits given vasopressin in oil alone. These results suggest that clonidine may be beneficial because it prevents ischemic microvascular injury in the renal outer medulla, an effect that may decrease tubular obstruction by lessening desquamation of damaged tubular cells or cell constituents into the tubular lumen. Clonidine may also decrease formation of obstructive hyaline casts in collecting ducts by blunting the kidney's response to vasopressin and increasing tubular fluid flow rate.

Acute Kidney Injury↗
PubMed1980

Comparison of remedial treatments for cursive handwriting of fourth-grade students.

Fourth-grade students participated in a study to investigate 4 methods of cursive handwriting instruction. Groups were rated by two independent raters on 5 handwriting characteristics. Poor and average writers received one of 4 taped methods. Two pretests, 8 training trials, and 1 posttest were administered. The K-sample binomial test of equal proportions and post hoc multiple comparisons in sample proportions for tests of homogeneity were used to analyze the data. Significant differences were found among the methods on 4 of the 5 characteristics among poor writers. For poor writers, the highest proportions of improvement were noted using 1 of 3 methods. Significant differences were found on 2 of the 5 characteristics for average writers.

Child↗
PubMed1980

Epidermal growth factor stimulation of human breast cancer cells in culture.

Epidermal growth factor (EGF), a polypeptide found in human and animal blood and secretions, has been found to stimulate a variety of tissues in vitro including normal and malignant rodent mammary epithelium and human breast epithelial cells and fibroadenoma. We have studied the influence of EGF on malignant human breast tissue with a model system comprising human breast carcinoma cells growing in tissue culture. EGF stimulated growth of MCF-7 cells in serum-free medium. After 7 days in culture, a 2-fold increase in cell number and DNA content and a 3-fold increase in total protein were observed in cells incubated with EGF (10 ng/ml). As little as 0.01 ng/ml of EGF stimulated growth; 10 ng/ml was maximal. EGF effects on growth were noted for cells plated at a high as well as sparse (cloning) density. EGF also stimulated the rates of thymidine, uridine, and leucine incorporation into macromolecules in a dose- and time-dependent fashion. Stimulation of uridine and leucine incorporation was evident by 3 hr, whereas EGF stimulation of thymidine incorporation was delayed until 12 to 18 hr. EGF increased the proportion of cells active in DNA synthesis by nearly 2-fold. The combination of optimal concentrations of insulin (also a growth factor for these cells) and EGF did not stimulate growth above that seen with either hormone alone, suggesting a common step in their mechanism of action. The EGF effect was not dependent on the presence of serum and was not enhanced by dexamethasone as reported for other types of cells. EGF had no effect on another human breast cancer cell line, the MDA-231. These studies suggest that growth of some human breast cancers may be influenced by EGF.

Animals↗
PubMed1979

GABA receptor control of parasympathetic outflow to heart: characterization and brainstem localization.

Blockade of gamma-aminobutyric acid (GABA) receptor function by direct microinjection of the GABA receptor antagonist bicuculline into the nucleus ambiguus of the brainstem produced a marked, dose-related depression of heart rate and blood pressure which was mediated by the vagus nerve. This effect was not obtained in other regions of the brainstem and was reversed by the GABA receptor agonist muscimol. These data indicate that the nucleus ambiguus may be the site of a GABA receptor-mediated inhibition of vagal outflow.

Animals↗
PubMed1975

The effect of timeout on performance on a variable-interval schedule of electric-shock presentation.

Responding was maintained in squirrel monkeys under variable-interval schedules of electric shock presentation when a period of timeout followed each response-dependent shock. Response rate decreased when timeout duration was decreased, and responding ceased when timeout was eliminated. These results indicate that under certain conditions, a shock-free period following each response-produced shock is necessary to maintain responding.

Journal Article↗
PubMed1975

Behavioral contrast in the pigeon: a study of the duration of key pecking maintained on multiple schedules of reinforcement.

Pecks on an operant key were reinforced on either multiple variable-interval variable-interval or multiple variable-interval extinction schedules of reinforcement. The stimuli that signalled the multiple-schedule components were located on a second key (signal key), and a changeover delay prevented reinforcement of signal key-peck-operant key-peck sequences. No behavioral contrast was observed on the operant key, and appreciable responding to the signal key occurred during the variable-interval component of the multiple variable-interval extinction procedure. Peck durations on the signal key were markedly shorter than peck durations on the operant key. Moreover, most responses on the signal key occurred just after the multiple-schedule components changed. These data support an account of behavioral contrast in terms of the summation of pecks that are separately controlled by stimulus-reinforcer and response-reinforcer dependencies, and suggest that the stimulus-reinforcer dependency is responsible primarily for local contrast. In addition, the data suggest that pecks that are controlled by these two dependencies may belong to topographically different classes.

Journal Article↗