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Biomedical subjects

J Cook

Publications and source records attributed to J Cook.

At least 73 records · Page 4Linked to original sources
PubMed1985

The interaction between benzodiazepine antagonists and barbiturate-induced cerebrovascular and cerebral metabolic depression.

It has been reported that pentobarbital facilities binding to benzodiazepine receptors binding at anesthetic concentrations and that this action may play a role in the anesthetic potency of this barbiturate. The interaction between pentobarbital and benzodiazepine receptors was tested with Ro 15-1788 which is reported to be a pure benzodiazepine antagonist and 3-hydroxymethyl-beta-carboline (3-HMC), an antagonist which has inverse activity alone. Cerebral blood flow (CBF) and cerebral oxygen consumption (CMRO2) were measured in rats after injections of pentobarbital with and without the antagonists. Pentobarbital produced dose-dependent decreases in cerebral blood flow and cerebral oxygen consumption at 15 and 30 mg/kg. The antagonist Ro 15-1788 (10 mg/kg) stimulated cerebral blood flow and cerebral oxygen consumption alone but did not alter the cerebral depression produced by pentobarbital. The cerebral metabolic stimulation produced by Ro 15-1788 was unexpected since the drug is reported to be a pure antagonist without agonistic activity, but the lack of effect on pentobarbital-induced cerebral depression is consistent with other reports. 3-Hydroxymethyl-beta-carboline at 10 mg/kg did not stimulate cerebral blood flow and cerebral oxygen consumption but significantly antagonized the decrease in cerebral oxygen consumption produced by 15 mg/kg pentobarbital. 3-Hydroxymethyl-beta-carboline had no significant effect on decreases in cerebral blood flow and cerebral oxygen consumption produced by phenobarbital, a barbiturate which is reported not to alter binding to benzodiazepine receptors. The ability of 3-HMC to antagonize the effects of pentobarbital would be consistent with an action of both drugs at the benzodiazepine receptor but not by altering binding to an endogenous receptor.

Animals↗
PubMed1985

Mouse monoclonal antibodies to the human C3b receptor.

Mouse monoclonal antibodies were raised against the human C3b receptor (CR1) molecule that had been purified from solubilized erythrocytes membranes. Four hybridomas were selected, cloned and expanded because their supernatants reacted strongly with insolubilized CR1 by ELISA and intensely stained B-dependent areas of the spleen and glomerular podocytes by indirect immunofluorescence. The four monoclonal antibodies, named J3D3, J8B10, J3B11 and J7C2, were IgG1 immunoglobulins. J3D3 immunoprecipitated two protein bands of apparent mol. wts 200,000 and 220,000 from 125I-surface-labeled human erythrocytes, which correspond to the two major allotypic forms of CR1. By indirect immunofluorescence, monoclonal antibodies stained polymorphonuclear leucocytes (PMN), most peripheral blood B-cells and a small subset of peripheral blood T-cells. J3D3 bound to CR1 on erythrocytes, PMN and lymphocytes with an affinity of 1-3 X 10(9) M-1 and recognized 170-1330 antigenic CR1 sites with an average of 740 sites/erythrocyte in 100 healthy individuals, approx. 50,000 sites/PMN and 15,000 sites/lymphocyte. There was a bimodal distribution of CR1 numbers on erythrocyte in the normal population. The four monoclonal antibodies similarly inhibited CR1-mediated decay of preformed cell-bound alternative- and classical-pathway C3 convertase sites. Two antibodies, J3D3 and J3B11, inhibited C3b-dependent rosette formation with lymphocytes, although much less efficiently than F(ab')2 polyclonal anti-CR1 antibody. Differences that were observed in the relative capacity of the antibodies to inhibit some of the functions of CR1 and in their ability to compete for binding of 125I-J3D3 to CR1 on erythrocytes, suggested that they are directed against different epitopes on CR1. Monoclonal antibodies provide useful means to assess and analyze the biological and immunoregulatory functions of the C3b receptor.

Animals↗
PubMed1985

Synthesis and antiinflammatory and analgesic activity of 5-aroyl-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylic acids and related compounds.

5-Acyl-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylic acids and the homologous pyridine and azepine derivatives were synthesized and assayed for antiinflammatory and analgesic activity. 5-Benzoyl-1,2-dihydro-3H-pyrrolo-[1,2-a]pyrrole-1-carboxylic acid and the corresponding p-methoxy compound 74 were selected for evaluation as analgesic agents in humans on the basis of their high potency in the mouse phenylquinone writhing assay as well as on their minimal liability to elicit gastrointestinal erosion in rats on chronic administration. Extensive quantitative structure-activity relationship (QSAR) studies of the benzoylpyrrolopyrrolecarboxylic acids have demonstrated that the analgesic (mouse writhing) and antiinflammatory (rat carrageenan paw) potencies of these compounds are satisfactorily correlated with the steric and hydrogen-bonding properties of the benzoyl substituent(s). The 4-vinylbenzoyl compound 95, which was correctly predicted to be highly active in both assays on this basis, is undergoing advanced pharmacological evaluation in animals as a potential antiinflammatory agent.

Analgesics↗
PubMed1985

An evaluation of pneumatic orthoses in thoracic paraplegia.

Pneumatic orthoses were used to mobilise eight post-traumatic thoracic paraplegic males whose progress was monitored for two years. The pneumatic orthosis was more likely to be used than pelvic brace and calipers mainly due to increased support for the pelvis and the thoracolumbar spine. The effects of the orthosis and the mobilisation upon patient physiology were studied. Beneficial effects upon cardiovascular and respiratory systems were noted and increases in total body calcium after mobilisation were found. Contraindications to fitting the orthosis include severe spasms, obesity and scoliosis.

Adult↗
PubMed1985

Perinatal events which precede periventricular haemorrhage and leukomalacia in the newborn.

Ultrasound brain scans were obtained daily for the first 5 days after birth, on day 7 and then weekly until discharge from hospital in 86 babies during a 12-month period. The babies weighed less than 1501 g or were less than 34 weeks gestational age. Fifty-one (59%) had normal scans, 34 (40%) developed periventricular haemorrhage, and seven (8%) developed periventricular cysts (associated with periventricular haemorrhage in six). Factors associated with periventricular haemorrhage were perinatal hypoxia, acidosis, hypercapnia and hypoxia after birth. Babies who developed periventricular cysts (periventricular leukomalacia) were more likely to have been hypoxic at birth and in four of the seven there had been a maternal antepartum haemorrhage. The association of perinatal hypoxia with periventricular haemorrhage and leukomalacia suggests that intrapartum events may predispose to the onset of these lesions which then develop postnatally. Prevention of perinatal hypoxia may play an important role in diminishing the disability caused by these conditions.

Brain Diseases↗
PubMed1985

Persistent hypertransaminasemia as the presenting finding of childhood muscle disease.

Four children with isolated, persistent elevations of serum transaminases were investigated for hepatic disease and followed for 4 to 24 months before serum creatine kinase determinations were obtained and found to be markedly elevated. Evidence of muscle disease was obtained by close questioning, retrospectively, and mild abnormalities were found on physical examination. Review of laboratory tests in our center for 6 months revealed 30 additional cases of anicteric hypertransaminasemia (20% of those with elevated enzymes), only two of which were unexplained by the admitting diagnosis. Serum transaminase values are elevated in a variety of diseases of different organ systems. Creatine kinase determinations may provide the clue to the diagnosis of occult muscle disease in some children with unexplained anicteric hypertransaminasemia.

Adolescent↗
PubMed1985

Thymocyte cyclic AMP and cyclic GMP response to treatment with metabolites issued from the lipoxygenase pathway.

Evidence has been presented that cGMP is the second messenger for the lipoxygenase metabolites 15-HETE and LTB4 in the mouse splenocyte and thymocyte. Incubation of splenocytes with 10(-7) to 10(-9) M 15-HETE caused a slight decrease in cAMP levels and an increase in cGMP levels after 10 to 20 min. Mature PNA-, immature PNA+, and whole thymocytes treated with 10(-7) to 10(-10) M 15-HETE and 10(-11) M LTB4 showed an approximately 100% increase in cGMP production. In mixed lymphocyte reactions, 15-HETE- and LTB4-treated PNA+, PNA-, and whole thymocyte populations inhibited thymidine uptake by fresh allostimulated splenocytes. These results demonstrate that the eicosanoid-induced generation of suppressor cells follows a rise in lymphocyte cGMP levels.

Animals↗
PubMed1984

Increased frequency of diabetes mellitus in patients with bullous pemphigoid: a case-control study.

A case-control study was designed to assess the occurrence rate of primary diabetes mellitus (DM) in patients with bullous pemphigoid (BP) by retrospectively reviewing the records of our thirty histopathologically and immunopathologically proved cases of BP from the past 10 years. One hundred twenty patients were selected as controls, which included two names immediately before and two names immediately after each case of BP in our histopathology record book. The occurrence rate of primary DM prior to the administration of systemic corticosteroids was significantly higher in patients with BP than in the controls (20% and 2.5%, respectively; p = 0.004). Among patients over 50 years of age, this occurrence rate was again higher in patients with BP than in the controls (23% and 3.6% respectively; p = 0.02). This study suggests a higher than chance association of BP and primary DM.

Adolescent↗
PubMed1984

Structure of the proteolipid protein extracted from bovine central nervous system myelin with nondenaturing detergents.

As a basis for attempts to define the structures of the proteins within myelin, methods have been developed for their extraction and isolation in solutions of non-denaturing detergents. With use of solutions of deoxycholate or Triton X-100, up to 90% of the protein has been extracted from bovine CNS myelin, along with most of the phospholipid. The proteolipid protein has been purified in deoxycholate solutions by chromatography on a blue dye-ligand column, which retained all of the basic protein and 2',3'-cyclic nucleotide-3'-phosphodiesterase, and then on Sephacryl S300, which separated proteolipid protein from phospholipid and high-molecular-weight proteins. The proteolipid protein was isolated from Triton X-100 extracts of myelin by adsorption onto phosphocellulose resin, with subsequent elution by 0.5 M sodium chloride. Gel permeation chromatography was used as the final purification step. Sedimentation equilibrium experiments gave a monomer molecular weight of 134,000 +/- 8000 in deoxycholate and 145,000 +/- 17,000 in Triton X-100 solutions. On the basis of an apparent subunit molecular weight of 23,500 it was deduced that the native protein is probably hexameric. Above 0.2 gL-1 in Triton X-100 solutions and 0.5 gL-1 in deoxycholate solutions the protein aggregated. In deoxycholate solutions the protein adopts the highly helical conformation expected for an intrinsic membrane protein.

Animals↗
PubMed1984

Iron and blood donation.

Regular blood donors undergo a progressive decline in iron reserves, while some develop frank iron-deficient erythropoiesis. The prevalence of iron depletion is significantly higher in menstruating women and increases progressively as the rate of donation increases. While conventional screening programmes based on the haemoglobin are adequate to prevent the development of progressive iron deficiency anaemia, they provide no indication of the development of tissue iron depletion. Recent studies indicate an impairment in a number of physiological processes associated with iron depletion but the liabilities of mild iron deficiency have not been fully defined. While it would be desirable to avoid iron depletion in regular blood donors only a minority of the eligible population have been willing to provide the blood resources of the USA in the past, and many individuals who can maintain high rates of donation without developing iron deficiency anaemia would be eliminated. However, there is little doubt that continued efforts should be made to encourage a broader base of volunteer donors. Improved public awareness of the need for blood has made it possible to obtain 88 per cent of the total supply from donors who gave blood three or less times during the year, and only 13.4 per cent of men and 11 per cent of women made three of more donations (Table 6). Further, women under 46 years of age constitute only 1 per cent of all donors who give four or more times during the year. Until clear-cut evidence is obtained of the deleterious effects of a lack of iron, the low prevalence of depleted iron reserves in men and non-menstruating women donors seems acceptable. However, current blood banking practices place a disproportionate iron demand on menstruating women. Because of the additional burden of pregnancy in this donor group, efforts to reduce the prevalence of a lack of iron in the child-bearing female should be encouraged. The simplest approach would be to limit the rate of blood donation to a maximum of three per year. This also is a subgroup among whom the application of more specific screening procedures for iron deficiency can clearly be justified. Iron supplementation programmes are also an attractive approach in these people who are likely to be highly motivated. Neither of these approaches have been adequately evaluated at the present time.

Administration, Oral↗
PubMed1984

Distribution of immunoglobulin-bearing cells in the gut-associated lymphoid tissues of the turkey: effect of antibiotics.

Distribution of immunoglobulin (Ig)-bearing cells in the gut-associated lymphoid tissues of antibiotic treated and untreated control turkeys (Meleagris gallopavo) was compared. Antibiotic treatment was similar to a regimen used in commercial turkey production, which included preincubation dipping of fertile eggs in gentamicin solution, injection of turkeys with gentamicin at hatching, and inclusion of chlortetracycline in the diet. Tissues were examined from turkeys at 3, 7, 14, and 21 days of age with a direct immunofluorescence procedure. Cell distribution in control turkeys was as follows: In the bursa of Fabricius, IgA-carrying cells predominated at 3 days of age, but at later intervals, the 3 classes of Ig-bearing cells were in equal numbers. In the cecal tonsils, IgM- and IgA-bearing cells were in larger numbers at 3 days of age, whereas, the IgG-bearing cells were sparsely distributed. By 7 days of age, IgM cells became more numerous in the cecal tonsils and remained numerous until 21 days of age. At 3 days of age, IgA cells predominated in the small intestines and IgM cells predominated in the large intestine. At 7 and 14 days of age, IgM cells were more numerous in the small and large intestines, but by 21 days of age, IgA cell population equaled that of IgM. The IgG cells were generally sparse in the intestines. Antibiotic treatment often resulted in lower numbers of Ig-positive cells, especially those bearing IgM and IgA. Normal development of the bursa of Fabricius was also retarded in this group.

Animals↗
PubMed1984

Distribution of immunoglobulin-bearing cells in the gut-associated lymphoid tissues of the turkey: effect of oral treatment with intestinal microflora.

One-day-old turkeys (Meleagris gallopavo) were orally inoculated with the intestinal contents of an adult turkey, and the intestinal tissues were studied by immunofluorescence for immunoglobulin (Ig)-bearing cells at 3, 7, 14, and 21 days of age. Microflora inoculation increased numbers of Ig-bearing cells in the gut-associated lymphoid tissues; the most uniform effects were observed at 3 days of age. As the birds grew older, this uniformity in response to the microflora inoculation was not evident in all the tissues. In the bursa of Fabricius and the large intestine of the inoculated birds, IgM-bearing cells were more numerous throughout the study period. Compared with noninoculated control turkeys, IgA-bearing cells in the cecal tonsils, and IgG- and IgA-bearing cells in the small intestine were increased at all age intervals.

Aging↗
PubMed1983

lambda Phage cro repressor interaction with DNA.

We present here the complete identification of the resonances from the aromatic region of the 1H NMR spectrum of the cro repressor of the Escherichia coli lysogenic phage lambda. This was accomplished by the use of two-dimensional NMR analysis as well as specifically deuterated tyrosines. Not surprisingly, it shows that the published resonance assignment approached by more conventional methods by others includes substantial errors. The effect of complex formation with DNA was examined in the 1H NMR spectrum as well as in 19F NMR spectra from 3-fluorophenylalanine- or 3-fluorotyrosine-substituted cro repressors. The fluoro analogues show the practicality of using a structural gene cloned into an inducible system as a starting point to obtain both material and specific nuclear spin incorporation for NMR spectroscopy. The NMR data offer direct support for the speculative models of cro repressor-DNA complexes proposed from x-ray structure analysis on the protein alone.

Bacteriophage lambda↗
PubMed1983

The effect of H1 and H2 receptor antagonists on the dermographic response.

The effect on dermographic wealing of an H1 and H2 receptor antagonist was studied separately and in combination. a double-blind protocol was used and dermographism was measured as the diameter of weal response to a measured force. Both H1 and H2 antagonists had a small but non-significant effect, but the combination of H1 plus H2 antagonist had an approximately additive effect which was significant. Although this indicates a role for H2 receptors in dermographism it does not establish the degree of involvement, nor whether H2 antagonists necessarily have any advantage over a potent H1 blocker alone in the treatment of dermographism.

Adult↗
PubMed1983

The human C3b receptor.

The cellular receptor for the C3b fragment of the third component of complement is a 205,000 molecular weight glycoprotein expressed by erythrocytes, polymorphonuclear leukocytes, monocytes, B lymphocytes, a subset of T lymphocytes and glomerular podocytes. The receptor molecule is a potent inhibitor of complement activation by both the alternative and classical pathways. It serves as a cofactor in the proteolytic degradation of C3b bound to immune complexes. On neutrophils and monocytes, the receptor enhances immunoglobulin-dependent phagocytosis of opsonized particles and triggers internalization of soluble ligands bearing C3b. The number of C3b receptor molecules expressed on erythrocytes is genetically determined and was found to be low in patients with systemic lupus erythematosus: these abnormalities when associated with a low number of receptors in the kidney of patients with non-systemic lupus erythematosus nephritis may predispose to immune complex diseases.

Animals↗
PubMed1982

The varying tissue distribution of L-glutamic acid labelled at three different sites.

Methods using 5 and 6 enzymes were devised to synthesize L-[11C]glutamic acid (GA), labeled on the carboxyl group of either the alpha-(AGA) or gamma-(GGA) carbon atom. The distribution of the 11C-labeled AGA or GGA in rabbits was compared with that of L-[13N]glutamic acid. The results show that AGA was rapidly decarboxylated with loss of the 11C-label, and that GGA was also decarboxylated, but to a lesser degree. Thus, the radiolabel distribution may not reflect the distribution of the original compound. The results also demonstrate that positron labeled pharamaceuticals may be rapidly synthesized via complex enzymatic pathways.

Animals↗