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Biomedical subjects

R Cooper

Publications and source records attributed to R Cooper.

At least 145 records · Page 8Linked to original sources

Bacteriology of urinary tract stones.

It has been reported that up to half of renal stones and associated urine specimens have been positive on culture, and that up to 50% of such stones contain magnesium ammonium phosphate. In a prospective study using infrared and wet chemical analysis, we found positive cultures in only 7 of 132 renal, 5 of 105 ureteral and 6 of 21 bladder stones obtained surgically and handled with sterility. Of the culture positive calculi only 43% from the kidney, none from the ureter and 50% from the bladder contained detectable magnesium ammonium phosphate. However, magnesium ammonium phosphate was detectable in 20% of renal, 2% of ureteral and 27% of bladder stones with negative cultures. Of the culture positive renal and ureteral calculi 42% were predominantly calcium phosphate and 17% were predominantly calcium oxalate. For culture negative stones 25% and 51% from the kidney, and 15% and 82% from the ureter were composed of predominantly calcium phosphate and calcium oxalate, respectively. Among the culture positive stones, related positive urine cultures were noted in 100% of the renal, 20% of the ureteral and 50% of the bladder cases, compared to 26%, 10% and 27%, respectively, of culture negative calculi. The same organism was found in the stone and urine in only 38% of the cases. The lower frequency of positive urine cultures, of stones with magnesium ammonium phosphate, and especially of culture positive renal and ureteral stones (5%) than in previous reports suggests that stone culture may be of less value than indicated previously, except for bladder calculi and large renal stones, such as the branched type.

Adult↗

Gene delivery and expression mediated by an integrin-binding peptide.

The ability to transfer sufficient DNA to specific target cells remains one of the main limitations to the development of gene therapy. For this reason much attention is being paid to the development of new gene delivery systems, both viral and non-viral. We describe gene transfer with a polycation-DNA complex which contains an integrin-binding domain. Integrin-mediated gene delivery has several potential advantages. Such complexes are less likely than other receptor-mediated gene delivery complexes to be constrained by the size of the complex. The ligands are small peptides, resembling naturally occurring integrin ligands, which minimises the possibility of complexes inducing an immune response in vivo.

Amino Acid Sequence↗

Familial resemblance for anthropometric measurements and relative fat distribution among African Americans.

Obesity has emerged as a major public health problem in the African-American community and its determinants are poorly understood. The purpose of this study was to examine familial patterns of the degree of heaviness and of regional fat deposits. Seven anthropometric measurements (height, weight, body mass index [BMI], waist and hip circumferences, waist-to-hip ratio and arm circumferences) were examined in a population sample of African-American nuclear families recruited from the Chicago area. Participants included 162 parent pairs and 114 sets of siblings (a total of 295 sons and daughters). Adjustments to correct for the effect of age and sex were performed separately for parents and siblings and the residuals were transformed to normalized z-scores to calculate intraclass correlations between family members. With the exception of waist-to-hip ratio, all variables showed positive familial resemblance, although the degree and level of statistical significance varied by type of relationship. Significant familial resemblance was observed for peripheral fat deposit, as measured by hip and arm circumferences (range: 0.04 for spouse pairs to 0.42 for daughter pairs), and obesity, as measured by BMI (range: 0.12 for spouses to 0.33 for mother-daughter comparison). Significant sex and generation differences were observed for height and hip. We conclude that African Americans exhibit significant familial resemblance for stature, degree of heaviness and regional fat deposits. Understanding the relative contributions of shared genes and shared environmental factors to the observed familial patterns could yield important insights into the origins of obesity in this high risk population.

Adolescent↗

Agmatine: an endogenous clonidine-displacing substance in the brain.

Clonidine, an antihypertensive drug, binds to alpha 2-adrenergic and imidazoline receptors. The endogenous ligand for imidazoline receptors may be a clonidine-displacing substance, a small molecule isolated from bovine brain. This clonidine-displacing substance was purified and determined by mass spectroscopy to be agmatine (decarboxylated arginine), heretofore not detected in brain. Agmatine binds to alpha 2-adrenergic and imidazoline receptors and stimulates release of catecholamines from adrenal chromaffin cells. Its biosynthetic enzyme, arginine decarboxylase, is present in brain. Agmatine, locally synthesized, is an endogenous agonist at imidazoline receptors, a noncatecholamine ligand at alpha 2-adrenergic receptors and may act as a neurotransmitter.

Adrenal Medulla↗

Lumbar and lumbosacral fusions using Cotrel-Dubousset pedicle screws and rods.

The first 50 consecutive patients stabilized with Cotrel-Dubousset rods for lumbar or lumbosacral fusions were followed for an average of 2 years. The occurrence of fusion, maintenance of alignment, and rate of hardware complications were examined. There were 28 men and 22 women, ages 18-87 years, and 133 vertebral levels. Twenty-nine sets of 5-mm, and 21 pairs of 7-mm, rods were placed. Two hundred and sixty-eight pedicle screws were used. Forty-eight out of 50 (96%) patients demonstrated successful arthrodesis after their initial procedure. One pedicle screw became separated from the rod. No rods migrated or broke. Seven (2.6%) pedicle screws bent and 3 (1%) broke. Large and small diameter Cotrel-Dubousset rods allowed short segment lumbar and lumbosacral fusion with a high degree of reliability.

Adolescent↗

Structure determination, pharmacological evaluation, and structure-activity studies of a new cyclic peptide substance P antagonist containing the new amino acid 3-prenyl-beta-hydroxytyrosine, isolated from Aspergillus flavipes.

Two novel cyclic heptapeptides, peptides 1a and 1c, were isolated from an Aspergillus flavipes culture, originally isolated from soil, and their structures established by chemical and spectroscopic evidence. Peptide 1a contains a new amino acid, 3-prenyl-beta-hydroxytyrosine, and is a competitive antagonist to substance P at the human NK1 receptor, with an inhibitor affinity constant (Ki) of 8 +/- 4 microM. Methylation of 1a gave the monomethyl derivative 1b, which is a more potent competitive antagonist, with a Ki of 0.12 +/- 0.03 microM at the human NK1 receptor. Herein we report the structure determinations of 1a and 1c, and some structure-activity results. Several analogs of 1a were prepared by derivatization and synthesis. Structure-activity results for these analogs confirmed that the 3-prenyl-beta-hydroxytyrosine moiety is critical for the biological potency of 1a and 1b.

Amino Acid Sequence↗

Familial aggregation of cardiovascular diseases in African-American pedigrees.

Familial aggregation of cardiovascular diseases and diabetes has been consistently demonstrated. However, virtually all of the evidence on the familial patterns of these diseases has come from white population samples. This study evaluates the level of familial excess risk among first degree relatives of 232 African-American pedigrees which included 1,420 individuals recruited from the Chicago, IL, area. Excess disease risk was observed among relatives (parents and offsprings) of affected probands compared to relatives of unaffected probands for coronary heart disease (odds ratio [OR] = 5.30; 95% confidence interval [CI] = 2.51-11.23); hypertension (OR = 1.98; CI = 1.41-2.80); stroke (OR = 3.24; CI = 1.08-9.70); and diabetes (OR = 2.95; CI = 1.55-5.62). The results of this study clearly show that coronary heart disease, hypertension, stroke, and diabetes aggregate in some African-American families and not others. Unaffected relatives of persons suffering from these diseases should be encouraged to have their blood pressure, lipid, and blood glucose levels measured at frequent intervals. These recommendations are particularly urgent in African-American communities because of the disproportionately high morbidity and mortality experienced from cardiovascular diseases and diabetes.

Adult↗

Hb FM-Fort Ripley: confirmation of autosomal dominant inheritance and diagnosis by PCR and direct nucleotide sequencing.

We describe a normal neonate who presented at four days of age with asymptomatic cyanosis. There was no evidence of cardiac or pulmonary abnormality and an extended family history included 13 other affected family members with asymptomatic cyanosis lasting one to three months. Polymerase chain reaction (PCR) amplification and direct nucleotide sequencing of the proband's G gamma chain gene revealed the mutation at codon 92 (CAC-->TAC) previously shown in haemoglobin FM-Fort Ripley (alpha 2 gamma G gamma 92 (F8) His-->Tyr). This is the first family with Hb FM-Fort Ripley reported so far. It demonstrates autosomal dominant inheritance of this condition and incomplete penetrance.

Amino Acid Sequence↗

Response from the ethics committee of Wolfson Children's Hospital (Jacksonville, Florida)

In summary, our HEC believes that the medical staff and family made an appropriate decision to withdraw therapy following a thorough procedural review. However, we also believe that had the HEC been reapproached on learning that the medical resident's comments were overheard, the unwanted and unnecessary governmental intrusion could have been avoided. Government intervention in this case led to legal entanglements as well as unwanted publicity. In the end, the parents' decision was upheld by the child protection agency and the courts. A more timely re-review with the HEC might have prevented a five-week delay in carrying out an ethically appropriate and permissible decision.

Confidentiality↗

Cucurbitacins, cell adhesion inhibitors from Conobea scoparioides.

In the course of screening natural products for antagonists of CD18-mediated cell adhesion, an extract with inhibitory activity was identified from the stem and leaves of Conobea scoparioides. Bioassay-guided fractionation led to a pure compound, identified by spectroscopy as cucurbitacin E [1]. Although many biological activities have been reported for the cucurbitacins, this is the first report of cell adhesion inhibition. Furthermore, closely related cucurbitacin analogues had different potencies, pointing to substructural features that are important for the activity.

Actins↗

Primer residues deposited by handguns.

There is much anecdotal information being disseminated, even offered in expert witness testimony, concerning the deposit of primer residues on the hands of persons in front of the muzzle of handguns. We present data for 9 mm and 380 Auto pistols and for a 38 caliber revolver depicting the procedure for obtaining wipings taken from targets representing the hands of a gunshot victim. These wipings from pork tissue were then analyzed for the primer residue metals antimony, barium, and lead. The data show that the two primary metals, antimony and barium, are deposited on the targets out to 4 feet for the pistols and out to three feet for the 38-caliber revolver. Testing will continue in actual cases with the gun and ammunition involved in the shooting.

Animals↗

Radiofrequency catheter ablation as a primary therapy for treatment of ventricular tachycardia in a patient after repair of tetralogy of Fallot.

A 20-year-old man with previous surgical repair of tetralogy of Fallot was admitted with hemodynamically significant ventricular tachycardia that was terminated with cardioversion. He was found at electrophysiological study to have easily inducible ventricular tachycardia that was mapped to the right ventricular outflow tract. Radiofrequency catheter ablation of the ventricular tachycardia focus rendered the patient's arrhythmia noninducible. This case represents a successful radiofrequency catheter ablation of a ventricular tachycardia focus associated with tetralogy of Fallot repair.

Adult↗

Angiotensinogen gene in human hypertension. Lack of an association of the 235T allele among African Americans.

The frequency of the 235T and 174M alleles of the angiotensinogen gene, previously reported to be associated with hypertension in Caucasians and Japanese, was compared between 57 hypertensive African Americans and 130 normotensive African Americans sampled as part of a community survey of hypertension in the Chicago area. The frequency of the 235T allele was unrelated to hypertension status (cases, 83%, control subjects, 82%), as was true for the 174M allele. Compared with Caucasians, the frequency of the 235T allele was twice as high in this African American population, while the frequency of the 174M allele was similar. Even higher frequencies of the 235T allele (93%) were noted in a sample of 122 Nigerians. It appears that the 235T allele is very common in populations of West African origin, although we found no evidence that it confers risk of hypertension.

Adult↗

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↗

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↗

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↗