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Biomedical subjects

A Saunders

Publications and source records attributed to A Saunders.

At least 19 recordsLinked to original sources
PubMed1990

Human immunodeficiency virus infection of monocytes: relationship to Fc-gamma receptors and antibody-dependent viral enhancement.

Antibodies that augment human immunodeficiency virus (HIV) infectivity of monocytes through Fc receptor (FcR) type III for IgG have been found in the blood of sero-positive patients and immunized chimpanzees. This study investigated the effect of acute and chronic HIV infection, as well as protein kinase C activators capable of up-regulating latent HIV, on the expression of these receptors. In addition, the frequency of this antibody-dependent enhancement (ADE) phenomenon was estimated using purified IgG from HIV-1 seropositive individuals at various clinical stages of infection. The existence of an FcR-dependent pathway for ADE of HIV-1 infection in peripheral blood monocytes and promonocytic U937 cells was confirmed in sera from a small subset of patients, and the phenomenon extended to FcR types I and II. The level of ADE activity was minimal, however, and no relationship between the presence or magnitude of the ADE phenomenon and clinical stage was uncovered. Finally, perturbations which activate a latent HIV infection were shown to concomitantly up-regulate FcR on infected and uninfected cells. This suggests a positive feedback loop linking up-regulation of latent infection, enhanced expression of low affinity HIV receptors such as FcR, and viral spread.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Final outcome of ursodeoxycholic acid treatment in 126 patients with radiolucent gallstones.

One hundred and twenty-six patients with radiolucent gallstones in 'functioning' gallbladders were treated with 8-10 mg ursodeoxycholic acid (UDCA) kg/day and followed to a treatment conclusion. Complete or partial gallstone dissolution was achieved in 74 (59 per cent). However, only 22 achieved complete gallstone dissolution, as judged by two normal oral cholecystograms; ultrasonograms were performed in 16 of these patients, and all were normal. UDCA was stopped in 76 patients: because of cystic duct obstruction (n = 12), severe biliary pain (n = 13), non-response (n = 25) or partial stone dissolution with arrested progress (n = 26). Life-table analysis showed that complete gallstone dissolution rates at four years were 25-30 per cent (two normal oral cholecystograms) and 17-19 per cent (two normal oral cholecystograms plus one ultrasonogram). All patients with complete gallstone dissolution had shown partial stone dissolution at 6-12 months; of those with partial stone dissolution at six months, only 25 per cent went on to complete gallstone dissolution, and then always within two years. Efficacy correlated inversely with stone size but not with age, sex, obesity or on-treatment saturation indices. Acquired surface gallstone calcification developed in 13 patients (life-table analysis 22 +/- 7 per cent at four years); none of these patients achieved complete gallstone dissolution and only five achieved partial stone dissolution. Thus, despite relatively high partial gallstone dissolution rates, the ultimate efficacy of UDCA in achieving complete gallstone dissolution is low.

Adult↗
PubMed1989

The effects of altered N-linked oligosaccharide structures on maturation and targeting of lysosomal enzymes in Dictyostelium discoideum.

We have examined the relationship of N-linked oligosaccharide structures to the proper targeting and proteolytic processing of two lysosomal enzymes, alpha-mannosidase and beta-glucosidase, in the slime mold Dictyostelium discoideum. Two different mutant strains, HL241 and HL243, each synthesize the same nonglucosylated, truncated, lipid-linked oligosaccharide precursor, Man6GlcNAc2. [3H]Mannose-labeled N-linked oligosaccharides were studied following their release from immunoprecipitated alpha-mannosidase and beta-glucosidase by digestion with peptide:N-glycosidase F. The oligosaccharides from both mutants resembled each other, but they were smaller and contained fewer anionic groups than those from the wild-type. The oligosaccharides from the mutants strains were reduced in sulfate and Man-6-P content, and all Man-6-P was in the form of acid-stable phosphodiesters. Pulse-chase radiolabeling experiments using [35S] methionine indicated that the precursor forms of both enzymes were smaller than wild-type, and that this difference was due solely to differences in N-linked oligosaccharides. The precursor forms of the enzymes were not over-secreted, but appeared to be proteolytically processed into mature forms at approximately 50% the rate of wild-type. This is mainly due to their prolonged retention in the rough endoplasmic reticulum, but, ultimately, both enzymes were properly targeted to lysosomes. These studies indicate that a reduction in the amount of sulfation, phosphorylation or size of the N-linked oligosaccharides in these mutants is not critical for the proteolytic processing and targeting of the lysosomal enzymes, but that these changes may influence their rate of exit from the rough endoplasmic reticulum.

Cell Fractionation↗
PubMed1989

Islet cell autoimmunity in type I diabetic patients after HLA-mismatched pancreas transplantation.

The aim of this study was to investigate a possible reenhancement of islet cell autoimmunity in type I (insulin-dependent) diabetic patients who received HLA-mismatched pancreas transplants from cadaveric donors and who underwent generalized immunosuppression. Circulating islet cell antibodies (ICA) and complement-fixing ICAs (CF-ICAs) have been tested at 1, 2, 3, 6, and 12 mo and at least once a year posttransplantation in 23 recipients of 25 transplants (22 simultaneous with kidney, 2 retransplants, 1 isolated; 23 segmental neoprene injected, 2 whole with enteric drainage). Patients were aged 35.3 +/- 1.9 yr with a duration of diabetes of 20.6 +/- 1.1 yr. Immunosuppression consisted of double or triple association of azathioprine, cyclosporin, and prednisone with or without temporary antilymphocyte globulins. The number of HLA-A and HLA-B compatibilities was none in 8 patients, one in 12 patients, two in 4 patients, and three in 1 patient. The mean follow-up was 4.0 +/- 0.4 yr/patient (range 0.4-7.2). ICAs were positive pretransplantation in 2 of 25 patients and reappeared 1-42 mo posttransplantation in another 7. In 6 patients, CF-ICAs were also positive. In 7 of 9 ICA+ patients the pancreas transplant failed; in 1 patient this occurred 4 mo before ICA reappearance, and in 6 patients it occurred 2-35 mo after the first detection of ICAs. Pancreas-transplant failure was significantly associated with the positivity for ICAs (P less than .05) and particularly for CF-ICAs (P less than .005). ICA positivity was transitory in 4 patients (2-27 mo) and persistent in the remaining 5 (up to 61 mo).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Lithium-induced thyroid disorders: a prevalence study.

A group of 116 lithium-treated patients (53 men, 63 women) with predominant diagnoses of affective disorders were systematically examined for the presence of thyroid disorders. Nine (7.8%) patients (2 men, 7 women) were found to suffer from hypothyroidism after a mean of 3.4 years of lithium therapy. An increase in thyroid-stimulating hormone without clinical hypothyroidism was noted in 2 (1.7%) patients (both men). Hyperthyroidism with a full-blown picture of thyrotoxic nodular goiter was noted in 1 woman, and temporary increases in thyroxine and triiodothyronine were noted in another woman. These findings are discussed in light of other studies.

Aged↗
PubMed1988

Feeding of partially hydrogenated fish oils to rats in comparison with partially hydrogenated soybean oil and refined rapeseed oil: a combined chronic oral toxicity and carcinogenicity study with in utero phase.

Partially hydrogenated fish oils (PHFO) have been widely used in human food products for many years, particularly in Europe, North and South America and in South Africa. Animal studies, mainly with rapeseed oil, suggested that erucic acid might be responsible for morphological changes in the myocardium. It was suggested that other members of the docosenoic (22:1) family of fatty acids might produce similar effects to those ascribed to erucic acid. Certain PHFO can contain relatively high levels of these other isomers. Thus it was decided to evaluate PHFO of differing 22:1 levels in comparison with partially hydrogenated soybean oil (PHSBO) and refined rapeseed oil (LEAR) in a rat life span study, preceded by a breeding period in which the experimental lipids were fed to male and female parents. Two commercially produced PHFO were selected to represent the lower (PHFO-L) and upper (PHFO-U) range of 22:1 contents, 4.3 and 13.8%, respectively. A third test oil was prepared from a 50:50 blend of these (PHFO-M) to provide and intermediary 22:1 level. The control PHSBO and LEAR contained 0 and 1.0% 22:1, respectively. These experimental oils were included in semi-purified diets at 8 and 16%, respectively, in the breeding and life span periods of the study, together with 4% of oil mixtures providing essential fatty acids (EFA). Specific pathogen free (SPF). Wistar weanling rats, 200 of each sex, provided the subjects for the breeding period. Sufficient numbers of offspring were obtained in suitable condition from each treatment group to allow selection of a total of 555 weanlings for allocation to the five dietary treatments of the life span period of the study. For the life span period of the study, which was terminated after 107 to 110 weeks of treatment, 50 subjects were allocated to each of the PHSBO, PHFO-L and PHFO-U dietary groups, and 50 males to each of the LEAR and PHFO-M groups. The remaining subjects were allocated to sub-groups for sacrifice four days or 26 weeks after introduction of the life span period diets. All life span group subjects were weighed and had their food intakes recorded, and were subjected to clinical examination, routinely. At designated stages, ophthalmoscopic examination of all subjects was carried out, and samples of blood and urine were obtained from sub-groups for laboratory analysis. All decedent and terminated life span group subjects were subjected to post mortem examination, with weighing of 16 organs.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1987

Characterization and clinical association of antibody inhibitory to HIV reverse transcriptase activity.

Reverse transcriptase activity of the human immunodeficiency virus (HIV) was blocked in vitro by immunoglobulin G (IgG) derived from certain individuals infected with this retrovirus. A heterogeneous immune response for inhibition of enzyme function was noted. Catalytic activity was depressed by 50% or more with the use of 10 micrograms of IgG from 11 of 16 HIV-seropositive asymptomatic carriers, but from 0 of 8 seronegative controls and 2 of 12 patients with acquired immune deficiency syndrome (AIDS) or the AIDS-related complex (ARC). The inhibitor was confined to the F(ab')2 fragment. It was not directed against the poly(rA) X oligo(dT) template, nor against major envelope or structural viral antigens, and did not cross-react with bacterial, avian, or other mammalian DNA polymerases. It did not correlate with recognition of polymerase antigens by radioimmunoprecipitation. Loss of this inhibitor may be associated with development of clinical disease. Ten asymptomatic HIV-seropositive carriers with high titers of IgG antibodies to reverse transcriptase were followed for a mean of 3 years. All of four lost inhibitory capability prior to development of AIDS or ARC, while titers persist in the six who remain clinically healthy.

AIDS-Related Complex↗
PubMed1987

Insulin dependent diabetes in Asians.

Type 1 diabetes is said to be extremely rare in children in India, where diabetes treated with insulin may be due to chronic pancreatic disease or malnutrition. To see whether typical type 1 diabetes occurred in Asian children in the United Kingdom, all known Asian children with diabetes in industrial West Yorkshire were ascertained. A total of 17 such children were studied; of these, seven were from three multiplex families and two fathers from these families had diabetes. All children were ketosis prone and developed diabetes while resident in the UK. There were significant increases in HLA-B8 and HLA-DR3 and increases in HLA-DR4 and HLA-DR3/DR4, while HLA-B15 was absent. Islet cell antibodies, either IgG or complement fixing, were present in four of 18 subjects tested, all of whom had disease of short duration. The prevalence of type 1 diabetes in Asian children aged 15 years or less in West Yorkshire was 36/100,000, assuming complete ascertainment. It is concluded that typical type 1 diabetes may occur in Asian children and this condition may be more common in families who have migrated to the UK.

Adolescent↗
PubMed1986

Anticystinuric effects of glutamine and of dietary sodium restriction.

We studied four patients with cystinuria to assess the effects of glutamine and dietary sodium on the urinary excretion of dibasic amino acids. In Patient 1, at an ad libitum dietary sodium intake of about 300 mmol per day, oral administration of glutamine led to reproducible and marked anticystinuria and antiornithinuria, whereas the excretion of lysine and arginine was not significantly affected. In Patient 2, at an ad libitum dietary sodium intake of about 150 mmol per day, no effect of glutamine could be demonstrated in studies lasting up to three weeks. Since the principal difference between Patients 1 and 2 was their dietary intake of sodium, Patient 3 was studied during dietary sodium intakes of 150 and 300 mmol per day. His cystine excretion was found to be higher at 300 than at 150 mmol per day. Glutamine suppressed his cystine excretion at a sodium intake of 300 mmol per day but had no effect at 150 mmol per day. When the effect of a further reduction in sodium intake alone was studied in a fourth patient, a decrease of 150 to 50 mmol per day was found to reduce cystine excretion markedly within 17 days. The low-sodium diet alone also reduced the excretion of lysine, arginine, and ornithine. We conclude that glutamine may reduce the excretion of dibasic amino acids at a high sodium intake but not at an intake of about 150 mmol per day. However, since a sodium-dependent excretion of the dibasic amino acids occurs at an intake down to about 50 mmol of sodium per day, dietary restriction of sodium can provide a safe approach to the treatment of cystinuria.

Administration, Oral↗
PubMed1985

A new method for separating mononuclear cells from whole blood.

The LeucoPREP tube, a new method for separating mononuclear cells from whole blood, is described. The LeucoPREP tube is a 7-ml glass tube which contains a polyester gel and a solution of a sucrose polymer and sodium diatrizoate (Histopaque, Sigma). Platelets, lymphocytes, and monocytes are separated from granulocytes and erythrocytes based on differences in density. Platelets are then removed from the mononuclear cells by washing. The yield, viability, and percentage of various cell subpopulations obtained from the LeucoPREP tube are equivalent to those obtained from standard Ficoll-based methods. However, the LeucoPREP tube is a faster, less technically demanding method than Ficoll. The major advantages of the LeucoPREP tube are that 1) whole blood is added directly into the tube, unlike Ficoll methods, in which the blood must be diluted and carefully layered; and 2) it requires a very short (10 min) centrifugation time. The LeucoPREP tube should be highly desirable to anyone processing many blood samples, for example, clinical laboratories.

Antibodies, Monoclonal↗
PubMed1979

Soluble di- and aminopeptidases in Escherichia K-12. Dispensible enzymes.

As part of a study of the peptidase content of Escherichia coli K-12, two peptidase-deficient amino acid auxotrophs isolated and characterized by Miller as pepD- (strain CM17) and pepD- pepN- pepA- pepB- pepQ- (strain CM89) were examined for the presence of several peptidases previously obtained from strain K-12 in this laboratory. The soluble fraction of each mutant was found to lack the broad-specificity strain K-12 dipeptidase DP and the strain CM89 fraction also lacked activity characteristic of the strain K-12 aminopeptidases AP, L, and OP; like strain CM17, strain CM89 contained the tripeptide-specific aminopeptidase TP. Strain CM89 (but not CM17) appeared to contain little if any activity attributable to the ribosome-bound aminopeptidase I of strain K-12. Whereas loss of DP, AP, OP, and aminopeptidase I activity may be attributed to the pepD-, pepB-, pepN-, and pepA- mutations, respectively, the reason for the loss of L activity remains uncertain. Grown responses of strain CM89 in liquid media containing di- or tripeptides were in accord with absence of enzymes catalyzing rapid hydrolysis of dipeptides. In synthetic liquid media supplemented with the required amino acids per se or with peptone, cultures of both CM strains grew more slowly than strain K-12 and produced smaller cell-yields than those produced by strain K-12.

Amino Acid Sequence↗