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Biomedical subjects

R Cooper

Publications and source records attributed to R Cooper.

At least 91 records · Page 5Linked to original sources
PubMed1994

WIN 66306, a new neurokinin antagonist produced by an Aspergillus species: fermentation, isolation and physico-chemical properties.

WIN 66306 (1a), a cyclic peptide containing a novel amino acid, was isolated as a neurokinin antagonist from an Aspergillus species, labelled SC230. Conditions that maximized the production of 1a were developed, leading also to production of the related compound WIN 68577 (2) and rosellichalasin (3). Both 2 and 3 were more active in the rat NK1 than in the human NK1 receptor binding assay, while 1a was more active at the human receptor with an inhibitor affinity constant of 7 microM.

Amino Acid Sequence↗
PubMed1994

Isolation and structure elucidation of two new calpain inhibitors from Streptomyces griseus.

Two new peptides, a diketopiperazine of N-methyltyrosine (1) and a tetrapeptide containing N-methyltyrosine (2), were isolated from an actinomycete strain Streptomyces griseus. These compounds inhibit the enzyme calpain in the micromolar range and were characterized on the basis of spectroscopic analysis, amino acid analysis and sequencing. The structure of the tetrapeptide N-methyltyrosyl-N-methyltyrosyl-leucyl-alanine (2), was also confirmed by total synthesis.

Calpain↗
PubMed1994

Benzomalvins, new substance P inhibitors from a Penicillium sp.

In the course of screening microbial broths for neurokinin receptor antagonists, a series of new benzodiazepines, benzomalvins A (1), B (2) and C (3), has been isolated from the culture broth of a fungus identified as a Penicillium sp. Benzomalvin A (1) showed inhibitory activity against substance P with Ki values of 12, 42 and 43 microM at the guinea pig, rat and human neurokinin NK1 receptors, respectively. Benzomalvins B (2) and C (3) were only weakly active. The structures of these compounds were determined by spectroscopic methods including MS measurements and NMR analysis.

Animals↗
PubMed1994

Peanut agglutinin binding by gastric mucosal epithelial cells in Helicobacter pylori associated gastritis.

Gastric biopsies (42) from patients with peptic ulcer disease were classified into Helicobacter pylori positive (32) and negative (10) groups, based on the results of tissue urease test and microscopic demonstration of spiral bacteria. A statistically significant difference in peanut agglutinin (PNA) binding between the two groups was observed, attributable to exposure of sialic acid residues on gastric epithelium in the H. pylori positive group. That the negative binding was due to sialic acid, was further confirmed by application of sialidase digestion technique. These results support the existing biochemical evidence for exposure of sialic acid residues on H. pylori colonized epithelium.

Adolescent↗
PubMed1994

Endoscopic ultrasound in the evaluation of Barrett's esophagus: a preliminary report.

OBJECTIVE: Endoscopic screening of Barrett's esophagus (BE) for dysplasia is imprecise and controversial. Endoscopic ultrasound (EUS) allows a detailed circumferential image of the esophageal wall. Our objective in this study was to assess the utility of EUS for surveillance in Barrett's esophagus. METHODS: Consecutive patients with proven BE undergoing endoscopy were evaluated with EUS. Esophageal wall thickness (EWT) was measured as the distance from the balloon-mucosal interface to the outermost hyperechoic line. EWT was determined as the average of all measurements done every 2-3 cm along the esophagus. Identical measurements were performed in a series of controls. RESULTS: Fifteen patients with BE and 13 control patients were studied. Two patients had focal submucosal thickening on EUS with EWTs of 10 mm and 7 mm. Surgical resection of the esophagus in these two cases with high-grade dysplasia revealed submucosal carcinoma at the area of EUS-documented thickening. The mean EWT of controls measured 2.6 mm, nondysplastic BE measured 3.3 mm, and BE with dysplasia measured 4.0 mm. The EWT of both dysplastic and nondysplastic Barrett's was significantly greater than that of the controls (p < 0.02, Student's t test). CONCLUSIONS: 1) As measured by EUS, the esophageal wall is significantly thickened in the columnar-lined portion of Barrett's esophagus. 2) EUS-detected focal thickening may represent submucosal carcinoma in areas of dysplasia and guide early surgery. Thus, EUS may play a role in evaluating the patients with dysplasia in Barrett's esophagus.

Adult↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1993

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↗