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Biomedical subjects

A John

Publications and source records attributed to A John.

At least 73 records · Page 4Linked to original sources

Suppressor T-cell deficiency in primary sclerosing cholangitis. Case and family study.

Primary sclerosing cholangitis is considered to be an autoimmune disease of the liver in which there is an association with the HLA phenotypes B8 and DR3 and in which circulating autoantibodies occur. Abnormalities of immune regulation may be present but whether or not they are primary or acquired is not known. This report is of a patient with primary sclerosing cholangitis who was homozygous for HLA B8 DR3, had a circulating antinuclear antibody, and a defect in nonspecific suppressor T-cell activity despite glucocorticosteroid treatment. Nevertheless, family studies revealed no evidence of an immunoregulatory defect in first-degree relatives despite the presence of Raynaud's phenomenon and malignancy in two sisters.

Adult↗

Effect of pigmentation on glutathione redox cycle antioxidant defense in whole as well as different regions of human cataractous lens.

'Reactive oxygen species', generated within the lens, are implicated in the deepening of nuclear pigmentation leading to browning of the human cataractous lens. The present study, which was carried out in senile brunescent cataracts, deals with changes in the antioxidant glutathione redox cycle defense system during the progression of browning (yellow to brown) in different regions of the human lens. A significant reduction in the levels of reduced glutathione was noted in the cortical and nuclear regions of the brown lens as compared to yellow lens, despite normal glutathione reductase activity. The rate limiting enzyme of the hexosemonophosphate shunt pathway, glucose 6-phosphate dehydrogenase, and the important oxidant scavenger enzyme, glutathione peroxidase, showed significant changes in opposite directions (glucose 6-phosphate dehydrogenase increased and glutathione peroxidase decreased), only in the cortical region of the brown lens as compared to yellow lens. The significance of the present findings in relation to the overall biochemical mechanisms underlying browning of the lens tissue in human cataracts is discussed.

Aged↗

Antigenic structure of chimeras of type 1 and type 3 polioviruses involving antigenic sites 2, 3 and 4.

Chimeric polioviruses have been made in which regions of the type 1 Sabin strain corresponding to antigenic sites 2, 3 and 4 have been replaced by the corresponding regions of the type 3 Sabin strain. Manipulation of one site or a component of it generally did not affect the reactions of the others, suggesting that they form independent structural features. The extent to which the inserted site expressed the antigenic properties of type 3 could be assessed by reaction with polyclonal or monoclonal antibodies, or by immunogenicity. Site 2 could be expressed on infectious virus and site 3 on heated non-infectious virus (C antigen), but not on the native virion. The results are consistent with the view that sites consisting of a continuous sequence of amino acids may be presented on chimeras, whereas more complex sites, such as site 4 or site 3 of the native virion, are transferred less readily from type 3 to type 1.

Amino Acid Sequence↗

Antigenic structure of chimeras of type 1 and type 3 poliovirus involving antigenic site 1.

Chimeric polioviruses have been prepared in which part of the antigenic site 1-encoding sequence of the Sabin strain of type 1 poliovirus has been replaced by sequences based on those found in the homologous region of the Sabin type 3 strain. The chimeras were analysed for their reaction with polyclonal and monoclonal antibodies raised against type 1 and type 3 viruses, and with polyclonal antipeptide sera, as well as for their immunogenicity in animals. The effectiveness with which the type 3 site was presented antigenically varied in ways which were partially predictable, based on the behaviour of type 3 mutants with monoclonal antibodies. However, other factors were implicated which may include conformational effects and other components of the site in addition to those altered in the chimeras. The ability of the chimeras to induce antibodies reacting with type 3 polioviruses paralleled their antigenic reactivity, and evidence is presented for the induction of strain-specific antibodies.

Animals↗

Treatment of outflow tract obstruction due to benign prostatic hyperplasia with the pollen extract, cernilton. A double-blind, placebo-controlled study.

Whilst prostatectomy remains the "gold standard" for the treatment of outflow tract obstruction due to benign prostatic hyperplasia, medical treatment--if only for symptomatic relief--appears to be an attractive alternative. Most of the pharmacological agents in use block the hormonal or the sympathetic neurological pathways that influence prostate growth and function. All of these drugs are known to have side effects. Sixty patients with outflow obstruction due to benign prostatic hyperplasia (BPH) were entered into a double-blind, placebo-controlled study to evaluate the effect of a 6-month course of the pollen extract, Cernilton. There was a statistically significant subjective improvement with Cernilton (69% of the patients) compared with placebo (30%). There was a significant decrease in residual urine in the patients treated with Cernilton and in the antero-posterior (A-P) diameter of the prostate on ultrasound. However, differences in respect of flow rate and voided volume were not statistically significant. It is concluded that Cernilton has a beneficial effect in BPH and may have a place in the treatment of patients with mild or moderate symptoms of outflow obstruction.

Aged↗

An engineered poliovirus chimaera elicits broadly reactive HIV-1 neutralizing antibodies.

The Sabin type 1 vaccine strain of poliovirus is probably the safest and most successful live-attenuated vaccine virus used in humans. Its widespread use since the early 1960s has contributed significantly to the virtual eradication of poliomyelitis in developed countries. We have reported previously the construction of an intertypic antigen chimaera of poliovirus, based on the Sabin 1 strain, and proposed that this virus could be modified to express on its surface antigenic determinants from other pathogens. We describe here the construction and characterization of a poliovirus antigen chimaera containing an epitope from the transmembrane glycoprotein (gp41) of human immunodeficiency virus type 1 (HIV-1). In antibody absorption experiments, the virus chimaera inhibited neutralization of HIV-1 by antipeptide monoclonal antibodies specific for the gp41 epitope and significantly reduced the group specific neutralizing activity of HIV-1-positive human sera. Rabbit antisera raised by subcutaneous injection of the polio/HIV chimaera in adjuvant was shown to be specific for HIV-1 gp41 in peptide-binding assays and by western blotting. Moreover, the antisera neutralized a wide range of American and African HIV-1 isolates and also inhibited virus-induced cell fusion. Monoclonal antibodies against the HIV-1 derived regions of the chimaera also neutralized HIV-1. These results establish the potential of using poliovirus for the presentation of foreign antigens and suggest that Sabin 1 poliovirus/HIV chimaeras could offer an approach to the development of an HIV vaccine.

Amino Acid Sequence↗

Reversion of the attenuated and temperature-sensitive phenotypes of the Sabin type 3 strain of poliovirus in vaccinees.

Isolates of type 3 poliovirus from vaccine-recipients were characterized in terms of virulence, sensitivity of growth to high temperatures, and differences in genome structure from the Sabin type 3 vaccine strain. These included point mutations in the region of the genome coding for the structural proteins and in the 5' noncoding region, and the presence of type 1 or type 2 poliovirus genomic sequences resulting from intertypic recombination. Isolates from healthy vaccinees resembled those from vaccine-associated cases of poliomyelitis in all of these properties. Suppression of the temperature-sensitive phenotype was strictly correlated with reversion to virulence in nonrecombinant type 3 strains. Recombinant isolates were more attenuated than expected, even when they had lost all mutations known to attenuate the type 3 vaccine strain.

Base Sequence↗

Reticulo-ruminal motility in cattle (Bos indicus) and water buffaloes (Bubalus bubalis) fed a low quality roughage diet.

1. The effect of A and B sequence contractions of the reticulo-rumen on passage rate of digesta was compared in buffaloes and cattle fed low quality rhodes grass. 2. Both species ate the same amount per unit body weight but buffaloes spent 53% more time ruminating than cattle. 3. Buffaloes had fewer A and B sequence contractions each day and the rate of these contractions during eating, ruminating and at rest were slower. 4. A larger pool of fine feed particles in the rumen of buffaloes, generated by extra ruminating activity was associated with the 30% shorter mean residence time of particulate matter in the forestomach compared with cattle. 5. It is concluded that the difference in the number and frequency of contractions between the species was insufficient to affect passage rate of digesta from the stomach.

Animals↗

Effect of vitamin A deficiency on nitrogen balance and hepatic urea cycle enzymes and intermediates in rats.

After 12 wk of feeding a 4-d nitrogen balance was carried out in 8 vitamin A--deficient and 8 pair-fed control rats to understand the effect of vitamin A deficiency on protein metabolism. Urea nitrogen (UN) was lower and amino nitrogen (AN) was higher in plasma of deficient animals than in pair-fed controls. No significant alteration in the nitrogen retention or in the general pattern of other nitrogen metabolites in plasma and urine was observed in vitamin A--deficient rats as compared to controls. However, there was a significant increase in the excretion of urinary ammonium nitrogen (Am-N) in relation to creatinine (CR). Activities of hepatic carbamoylphosphate synthase-I (CPS-I) and ornithine transcarbamoylase (OTC) were significantly lower in vitamin A--deficient animals than in control rats at the end of 13 wk of feeding. While the liver levels of ornithine and polyamines were significantly greater, that of glutamine was lower in vitamin A--deficient rats than in pair-fed controls. The results suggest that vitamin A deficiency leads to a reduced efficiency of urea synthesis pathway, thus accounting for the increased Am-N excretion seen in vitamin A deficiency.

Amino Acids↗

The temperature sensitivity of the Sabin type 3 vaccine strain of poliovirus: molecular and structural effects of a mutation in the capsid protein VP3.

The growth of the Sabin strain of type 3 poliovirus is reduced at high temperatures compared to that of its virulent precursor strain Leon. Recombinant viruses have been generated from infectious cDNA clones and demonstrate that the temperature-sensitive (ts) phenotype is mainly attributable to a difference in residue 91 of the virion protein VP3. Examination of non-ts mutants derived in vitro or in vivo reveals the existence of second site mutations some of which are clearly able to suppress the ts phenotype. The location of residue 91 of VP3, and of a number of candidate suppressor mutations, in the atomic structure of the virion suggests that the ts phenotype may result in destabilization of the particle and that the suppressors may function by stabilizing specific interfaces. It is not yet clear whether the ts phenotype is expressed at the level of the particle or in the form of defects in assembly or uncoating of the virion, or all three.

Amino Acid Sequence↗

[Improving the reproducibility of bone marrow culture by means of a salt-conditioned medium as a definite source of colony-stimulating activity].

Bone-marrow stem cell culture allows an insight into the regulatory system of normal and disturbed haemopoiesis. However, the prerequisite for it is that defined conditions of cultures are created. One step in this direction is the application of conditional media as a source of colony stimulating activity. The capacity of various conditioned media to stimulate proliferation and differentiation of human bone-marrow cells was examined and compared with the traditional feeder technique. In this respect the addition of 15% of umbilical cord conditioned medium proved to be well suited to achieve reproducible results.

Bone Marrow Cells↗

Evaluation of a colorimetric method for vitamin A estimation.

A simple colorimetric procedure for plasma vitamin A is evaluated, which does not require sophisticated or expensive equipment. Vitamin A values obtained with 30 human plasma samples and 11 liver samples obtained from lactating rabbits, using a colorimetric procedure based on Carr-Price reaction with ferric chloride and acetyl chloride were compared with those obtained with spectrophotometric and spectrofluorimetric micro methods. With widely varying plasma samples, the values showed a high degree correlation and good agreement. The intraassay variation was 3% which is in the acceptable range. The plasma samples could be analysed within 4 weeks and the reagents, were found to be stable, unlike some batches of trifluoro acetic acid (TFA).

Animals↗

Biostability of polyurethanes.

Aside from the medical requirements a material has to fulfill to qualify as biocompatible, for the bioengineer, who is involved in the design, construction and fabrication of prosthetic devices, the mechanical, physical and chemical properties of the material as well as its possible manufacturing procedures and, last but not least, its biostability are of the same importance. In the very aggressive biological environment, the material should behave inertly, showing no surface erosions, molecular chain disruptions, uptake of low molecular weight biological materials, local chemical imbalances, tendency to calcification or negative changes of mechanical properties. With regard to this aspect, different polyurethanes have been evaluated in-vitro and in-vivo as basic materials and already fabricated devices (blood pumps and heart valves). The comparison of the results stresses the necessity of further efforts to achieve a standardized test protocol for the prove of the biostability of polymers, containing appropriate, well-defined in-vitro and in-vivo test methods to establish the necessary data basa for the materials' clinical approval.

Animals↗

Seizure disorder in the men of a Veterans Administration nursing home.

This study examined the descriptive epidemiology of seizure disorder in 129 male residents of a Veterans Administration Nursing Home. Eighty-seven of the residents were institutionalized because of nonpsychiatric disorders (60 for chronic neurologic diseases, and 27 for other medical conditions). Forty-two were institutionalized because of a chronic psychosis (39 for schizophrenia, three for affective disorders). We determined for each resident an extensive clinical data base of 54 items including measures of hematologic, nutritional, metabolic and endocrine status, as well as continuing medications. In the nonpsychiatric group, 16 of the 87 men had a seizure disorder. In the psychiatric group, this proportion was only three of 42. The prevalence of epilepsy in the nonpsychiatric group was 20-40 times greater than in the aged-matched general population of men. In the nonpsychiatric group, the onset of seizures followed the onset of organic brain disease. Forty-five percent of seizure disorders occurred in men who had experienced a cerebrovascular accident, and 23% in men with other types of chronic brain disease. The seizures of the nonpsychiatric men had been observed to be generalized clonic-tonic in 45%, and partial complex in 22%. Ninety-four percent of the nonpsychiatric men with epilepsy received anticonvulsants, and none had experienced more than one seizure during the preceding year. Univariate statistical analysis of the 54 item data base showed that the occurrence of seizure disorder correlated inversely with age, blood urea nitrogen, serum creatinine and serum bilirubin, and directly with plasma testosterone, hemoglobin, use of anticonvulsants, and use of psychotherapeutic agents.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

The use of a monoclonal antibody for the determination of atrial natriuretic peptides in human plasma.

A monoclonal antibody (mab) directed against alpha-human atrial natriuretic peptides (alpha-hANP) was produced. Using this mab a radioimmunoassay for the determination of hANP-like immunoreactivity in human plasma was established. To demonstrate the possible application of this radioimmunoassay for clinical diagnosis, plasma levels were measured in healthy subjects and in patients with renal failure before and after hemofiltration or hemodialysis. Plasma levels in healthy subjects ranged between less than 30 and 124 pg/ml. Mean plasma concentrations of hANP-IR in uremic subjects were 324 pg/ml before and 113 pg/ml after hemofiltration or hemodialysis.

Adult↗

Alpha-h-ANP is the only form of circulating ANP in humans.

Alpha-human atrial natriuretic peptide (alpha-h-ANP) was purified to homogeneity from human plasma of healthy adults in a three-step procedure including immunoaffinity chromatography on immobilized monoclonal anti-alpha-h-ANP antibody (moab). A single peak of immunoreactivity was obtained after final reversed-phase HPLC and the amino acid sequence of the isolated material was identical to that of synthetic alpha-h-ANP. No further atrial peptides could be detected although the moab reacts with all biologically active peptides. It is therefore concluded that alpha-h-ANP is the only form of ANP circulating in human plasma.

Adult↗

The effect of condensed tannins on the site of digestion of amino acids and other nutrients in sheep fed on Lotus corniculatus L.

Sheep were used to evaluate the nutritional consequences of a low condensed-tannin concentration (22 g/kg dry matter (DM)) in lotus (Lotus corniculatus L.) (control group) compared with lotus given to sheep receiving intraruminal polyethylene glycol (PEG) infusion (PEG group). PEG selectively binds to tannins and prevents tannins from binding proteins. DM intakes (1430 (SE 28) g/d) and digestibility of energy (663 (SE 4.5) kJ/MJ intake) were similar for both groups but the apparent digestion of nitrogen was lower in the control sheep (0.70) than in the PEG sheep (0.78; P less than 0.001). The proportion of N apparently digested before the abomasum (i.e. in the rumen) was lower (P less than 0.05) in control sheep (0.12) than in PEG sheep (0.21; P less than 0.05). Rumen ammonia concentrations were lower (P less than 0.001) in control sheep than in PEG sheep. The proportion of neutral-detergent fibre (NDF) digested in the rumen was similar for both groups (0.48 (SE 0.012)) but less energy was digested in the rumen of the control (0.42) than of the PEG sheep (0.47; P less than 0.05). The flux of essential amino acids (EAA) through the abomasum of control sheep was 50% greater than that in PEG sheep; flux of non-essential amino acids (NEAA) was 14% higher in control than in PEG sheep. Apparent digestibility of EAA in the small intestine was similar for both treatments (0.67), but NEAA were less well digested in the control (0.55) than in the PEG sheep (0.69). The presence of tannins in the control group increased net apparent absorption of threonine (57%), valine (89%), isoleucine (94%), leucine (30%), tyrosine (41%), phenylalanine (93%), histidine (90%) and lysine (59%), and reduced NEAA absorption by 10%, compared with PEG sheep.

Abomasum↗