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Biomedical subjects

R Cooper

Publications and source records attributed to R Cooper.

At least 55 records · Page 3Linked to original sources

Race, income, and survival from breast cancer at two public hospitals.

BACKGROUND: Some studies have shown that adjustment for socioeconomic status reduces breast cancer survival differences between blacks and whites. The purpose of this study is to evaluate the effect of age, race, stage, treatment, and income status on breast cancer survival among women attending public hospitals in Chicago, Illinois. METHODS: Hospital Cancer Registry data on 887 black women and 265 white women with breast cancer onset between 1973-1985 were analyzed using Cox regression and Kaplan-Meier techniques. The purpose was to examine the effect of age, race, stage, treatment, and income on breast cancer survival. RESULTS: Black women with breast cancer were younger and poorer than white women with breast cancer. There were no significant differences between blacks and whites with regard to stage, estrogen receptor status, or type of treatment. Black women had lower 5-year breast cancer survival rates compared to white women (50.2% versus 60.2%; P = 0.05), and survival was lower when adjusted for stage and age. However, when adjusted for income in addition to stage and age, the effect of race on survival was reduced (from relative risk = 1.26; 95% confidence interval = 1.02, 1.57 to relative risk = 1.17%; 95% confidence interval = 0.95, 1.38). CONCLUSIONS: Income influences breast cancer survival differences between blacks and whites in this population.

Black or African American

Antidromic activation of a peptidergic pathway in the limbic system of the male rat.

Stimulation of the medial amygdaloid nucleus (AME) produces a long-latency and long-lasting inhibition of pyramidal cells in both the dorsal and the ventral hippocampus. The inhibition is blocked by a specific antagonist to vasopressin, which is a candidate neurotransmitter in the system. Antidromic activation of the AME from the hippocampus occurs with a latency suggestive of the conduction velocity of small diameter unmyelinated fibers. Immunocytochemistry for vasopressin reveals small diameter, unmyelinated immunoreactive fibers in the vicinity of the stimulating electrode in the hippocampus, and immunoreactive cell bodies in the vicinity of the recording electrode in the AME.

Amygdala

Performance of two films for densitometry of retinal photographs.

The relative performance was determined of two different photographic films (Kodak Panatomic-X and Kodak Technical Pan) for densitometry readings from retinal photographs of patients who had or were suspected of having glaucoma. The raw data from the two films were significantly different. The high contrast film was particularly sensitive to external variables; however, when normalised in terms of the standardised deviation, the data from the two films were comparable (P < 0.005). We also measured the pattern of nerve fibre layer loss using digital image analysis of red-free photographs of normal, ocular-hypertensive, glaucoma-suspect and glaucomatous eyes. Several mathematical techniques were used to characterise the data from each eye and then to compare these data to the mean photographic density of the normal eyes. Results showed that it was possible to separate normal eyes from glaucomatous eyes. The highest sensitivity achieved was 100% for right and 88% for left eyes, and the highest specificity was 100% for both eyes.

Adult

Deletion of an immunodominant Trypanosoma cruzi surface glycoprotein disrupts flagellum-cell adhesion.

Null mutants of the Trypanosoma cruzi insect stage-specific glycoprotein GP72 were created by targeted gene replacement. Targeting plasmids were constructed in which the neomycin phosphotransferase and hygromycin phosphotransferase genes were flanked by GP72 sequences. These plasmids were sequentially transfected into T. cruzi epimastigotes by electroporation. Southern blot analyzes indicated that precise replacement of the two genes had occurred. No aberrant rearrangements occurred at the GP72 locus and no GP72 gene sequences had been translocated elsewhere in the genome. Western blots confirmed that GP72 is not expressed in these null mutants. The morphology of the mutants is dramatically different from wild-type. In both mutant and wild-type parasites, the flagellum emerges from the flagellar pocket. In the null mutant the normal attachment of the flagellum to the cell membrane of the parasite is lost.

Amino Acid Sequence

Potency estimation of mivacurium: comparison of two different modes of nerve stimulation.

We have assessed the potency of mivacurium, a new non-depolarizing neuromuscular blocker, using two different modes of nerve stimulation in patients anaesthetized with thiopentone, fentanyl and nitrous oxide in oxygen. The force of contraction of adductor pollicis was measured after single twitch stimulation at 0.1 Hz or train-of-four stimulation (TOF) at 2 Hz every 10 s. Dose-response curves were constructed using a single-dose method for each mode of stimulation. The ED50 and ED95 were 43 micrograms kg-1 and 83 micrograms kg-1, respectively, for the single twitch responses and 34 micrograms kg-1 and 66 micrograms kg-1, respectively, for the first response of the TOF stimulation. The difference between the ED95 doses was not significant (P = 0.051), but the difference between the ED50 doses was significant (P = 0.03), suggesting greater sensitivity of the neuromuscular junction using TOF stimulation. The results show that the information obtained using single twitch stimulation at 0.1 Hz is not the same as that obtained from the first response of the TOF stimulation.

Adolescent

Promutagenic methylation damage in liver DNA of mice infected with Schistosoma mansoni.

Male and female BK-TO mice were infected with different numbers of Schistosoma mansoni cercariae under standard environmental conditions. Promutagenic methylation damage (O6-methyldeoxyguanosine; O6-MedG) was detected in liver DNA, but not in kidney, spleen or bladder DNA of infected animals. It was shown that levels of hepatic O6-MedG increased with increasing intensities of schistosomal infection. Possible mechanisms of action are discussed. These include the activating effects of schistosomes and their products on murine macrophages and subsequent endogenous formation of N-nitroso compounds by the activated macrophages.

Animals

Gene deletion suggests a role for Trypanosoma cruzi surface glycoprotein GP72 in the insect and mammalian stages of the life cycle.

We have explored the biological function of a surface glycoprotein (GP72) of Trypanosoma cruzi by studying a null mutant parasite, generated by targeted gene deletion. GP72 deletion affected parasite morphology in several stages of the life cycle. Insect midgut (epimastigote) forms had a detached flagellum (apomastigote) in the null mutant. The abnormal flagellar phenotype persisted during development of the infective (metacyclic) forms but there was no impairment in the acquisition of complement resistance, sialidase expression or cell infectivity. The GP72 null mutant could efficiently infect and proliferate in mouse macrophages and non-phagocytic L6E9 cells. The mammalian stages of the life cycle also showed major morphological abnormalities. During early subcultures in L6E9 cells, few extracellular fully flagellated forms, expressing markers characteristic of trypomastigotes, were seen. The extracellular population consisted almost exclusively of rounded forms with short flagella (micromastigote), which expressed an amastigote-specific surface marker and no sialidase. The propagation of the parasite was not affected, despite the apparent lack of the trypomastigote forms, which are thought to be primarily responsible for cell invasion. After some subcultures, the extracellular population changed to about equal numbers of micromastigotes and a range of flagellated forms that still did not include true trypomastigotes. Instead, the kinetoplast remained close to the nucleus and the flagellum emerged from the middle of the cell (mesomastigote). Half of the flagellum adhered to the cell body and the remainder was free at the anterior end. In Triatoma infestans, the survival of the mutant was dramatically reduced, suggesting that either GP72 itself, or the altered properties of the flagellum, were critical for establishment in the insect vector.

Animals

Anthrotainin, an inhibitor of substance P binding produced by Gliocladium catenulatum.

Substance P (SP) is an undecapeptide belonging to a family of chemically related neurotransmitters and neuromodulators known as neurokinins. In our search for SP antagonists, we screened microbial broth extracts for the ability to inhibit radiolabeled SP binding to membranes prepared from rat forebrain. Anthrotainin was isolated from a fungal culture and determined to be a novel tetracyclic compound, with an IC50 of 3 microM against [125I]SP. The structure, spectroscopic, chemical, and pharmacological properties of anthrotainin are presented.

Animals

Fiscalins: new substance P inhibitors produced by the fungus Neosartorya fischeri. Taxonomy, fermentation, structures, and biological properties.

Three new compounds, named fiscalins A, B, and C, were found in culture broth produced by a Neosartorya fischeri. These compounds inhibit the binding of radiolabeled substance P ligand to the human neurokinin (NK-1) receptor, with Ki values of 57, 174, and 68 microM, respectively. Detailed spectroscopic and amino acid analyses led to the elucidation of structures for the three fiscalins. The structures contain an indolyl moiety linked to an athranilic acid derived tricyclic system. The absolute configuration of fiscalin A was determined by X-ray crystallography and chiral amino acid analysis. The presence of fiscalins was detected directly in crude cellular extracts using LC-MS methods.

Cells, Cultured

Comparison of excretory urography and ultrasonography for detection of experimentally induced pyelonephritis in dogs.

Pyelonephritis was experimentally induced in 10 clinically normal dogs by nephropyelocentesis and introduction of Proteus mirabilis into the randomly chosen right or left renal pelvis. Dogs were examined by nephrosonography and excretory urography before and 2 weeks after infection. The major nephrosonographic findings of pyelonephritis were renal pelvic dilatation, usually with proximal ureteral dilatation, and a hyperechoic mucosal margin line within the renal pelvis, proximal portion of the ureter, or both. In addition, at least one or more of the following were observed: generalized hyperechoic renal cortex, focal hyperechoic areas within the medulla, and focal hyperechoic or hypoechoic cortical lesions. Interpretation of excretory urograms resulted in 3 false-negative and 1 false-positive conclusions, compared with the histologic findings. Interpretation of nephrosonograms resulted in 2 false-negative and no false-positive conclusions. Of the kidneys with histologic evidence of pyelonephritis, 73% were detected by excretory urography, whereas 82% were detected by nephrosonography. Nephrosonography appeared to be useful for detection of mild to moderate cases of acute pyelonephritis that may be be interpreted as such by excretory urography.

Animals

Survival of heart failure patients with preserved versus impaired systolic function: the prognostic implication of blood pressure.

The impact of impaired versus preserved systolic function on survival of patients with heart failure was investigated in 78 patients with decompensated heart failure. Patients were classified on the basis of their left ventricular systolic performance, as defined by fractional shortening (FS); group I (n = 56) had impaired systolic function (FS less than 24%) and group II (n = 22) had preserved systolic function (FS greater than or equal to 24%). Mean ejection fraction was 15 +/- 5% and 40 +/- 13% for these groups, respectively. By the end of 48 months, 36 patients in group I had died compared with only 22 patients in group II (p less than 0.05). Both systolic and diastolic blood pressure were significantly lower in the deceased patients compared with the survivors in group I (p less than 0.05). There was a trend for an opposite direction in the relationship of blood pressure to mortality in group II. We conclude that the prognosis of patients with heart failure and preserved systolic function is more favorable than that of those with impaired function, and that blood pressure may have a differential prognostic meaning in the two groups.

Blood Pressure

Effect of doxapram on the rate of recovery from atracurium and vecuronium neuromuscular block.

We have studied the effect of doxapram on the rates of spontaneous and neostigmine-induced recovery from neuromuscular block with atracurium and vecuronium, by measurement of the time to recovery of T1 (first twitch in the train-of-four) from 25 to 75% of control (recovery index, RI). After each neuromuscular blocking drug, RI was measured without administering either doxapram or neostigmine (control group), or after administration of doxapram 1 mg kg-1, neostigmine 50 micrograms kg-1 or a combination of doxapram and neostigmine, in groups of 10 patients. RI was significantly longer after vecuronium in the presence of doxapram compared with control (20.1 min vs 14.6 min). There was no significant difference in the RI after atracurium in the presence of doxapram compared with control (12.5 min vs 11.8 min) or when neostigmine was administered with or without doxapram (2.4 min vs 2.4 min, respectively after vecuronium; 3.3 min vs 2.9 min, respectively, after atracurium).

Adolescent

Comparison of intubating conditions after administration of Org 9246 (rocuronium) and suxamethonium.

We have assessed intubating conditions after administration of Org 9426 (rocuronium) 600 micrograms kg-1 at 60 or 90 s in groups of 20 patients anaesthetized with thiopentone, nitrous oxide in oxygen and small doses of fentanyl, and compared the data with those obtained after suxamethonium 1 mg kg-1 in similar groups of patients. The influence of prior suxamethonium administration on the potency of Org 9426 was studied also by constructing a dose-response curve. Intubating conditions after Org 9426 were found to be clinically acceptable (good or excellent) in 95% of patients at 60 s and in all patients at 90 s and in all patients at both times after suxamethonium. The average time for the onset of block following Org 9426 at this dose was 89 s (which is shorter than with any of the currently available non-depolarizing neuromuscular blocking drugs); the duration of clinical relaxation (25% recovery of twitch height) 30 min. Prior administration of suxamethonium did not appear to influence the potency of Org 9426.

Adolescent

Dose-response relationships for neostigmine antagonism of vecuronium-induced neuromuscular block in adults and the elderly.

We have studied the dose-response relationship for neostigmine in 36 adult (ages 18-50 yr) and 36 elderly (ages > 70 yr) subjects during antagonism of neuromuscular block induced by vecuronium. All patients received vecuronium 0.08 mg kg-1 and neuromuscular block was monitored mechanomyo-graphically using the train-of-four (TOF) mode of stimulation. Six patients of each age group were allocated randomly to receive neostigmine 5, 15, 25, 35 or 45 micrograms kg-1 or saline at 10% recovery of T1 (first response in the TOF). TOF ratios were recorded continuously over the next 10 min and the values at 1-min intervals from 5 min onwards were used to construct the dose-response relationships. There was a significant difference (P < 0.05) in the time to spontaneous recovery of T1 to 10% between the adults (24 (SD 5.5) min) and the elderly (33 (7.8) min). Dose-response curves for neostigmine were parallel in the two age groups, but those for the elderly were significantly to the right of the curves for the adults. This suggests an apparently lesser relative potency of neostigmine, or the requirement of a larger dose, in the elderly for attaining antagonism of a moderately intense vecuronium block at the same time as in adults.

Adolescent

A phase II study of recombinant interleukin-2 with or without recombinant interferon-beta in non-Hodgkin's lymphoma. A study of the Cancer and Leukemia Group B.

Interleukin-2 (IL-2) and interferon-beta (IFN-beta) have demonstrated activity against lymphoid malignancies, presumably mediated by the augmentation of lymphokine-activated killer (LAK) cell and natural killer (NK) cell activity. There is in vitro and in vivo evidence to suggest that the combination of IL-2 and IFN-beta is synergistic. The Cancer and Leukemia Group B (CALGB) conducted a randomized phase II trial of IL-2 with or without IFN-beta in 49 patients with relapsed or refractory non-Hodgkin's lymphoma (NHL). Overall toxicity was severe, with 17 patients experiencing life-threatening toxicity. Three patients had treatment-related deaths. Responses were noted in seven patients (17%). There were no meaningful differences between treatment arms in toxicity profile, response rate, or modulation of in vivo NK and LAK activity. We conclude that IL-2 with or without IFN-beta is not effective therapy for NHL in the doses and schedule used in this study.

Adult