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Biomedical subjects

S James

Publications and source records attributed to S James.

At least 127 records · Page 7Linked to original sources

Induction of protective immunity against Schistosoma mansoni by a nonliving vaccine. IV. Fractionation and antigenic properties of a soluble adult worm immunoprophylactic activity.

An aqueous buffer-soluble, nonparticulate fraction of adult Schistosoma mansoni worms (SWAP) was separated by gel filtration on Ultragel AcA-34, and portions of the eluate were tested for their capacity to induce protective immunity against cercarial challenge when administered intradermally to mice in combination with the adjuvant BCG. All of the immunogenic activity was found in a single peak of protein excluded in the void volume of the column. This same fraction was determined by SDS-PAGE and Western immunoblotting to be unique in that it contained a component of Mr (X 10(-3) 97 (97,000) recognized monospecifically by antibodies from mice vaccinated with unseparated SWAP plus BCG. Similarly, the protective fraction was unique in possessing the capacity to elicit 24 hr delayed footpad swelling responses, as well as lymphokine production, in SWAP-BCG-immunized mice. These results suggest that the immunogenic activity of SWAP resides in a restricted population of molecules, and possibly in the 97,000 antigen detected with antibodies from vaccinated animals. Because both the protective capacity of unfractionated SWAP and the serologic reactivity of the 97,000 antigen are sensitive to digestion with protease, it is likely that the immunologic activity of these molecules is dependent on peptide-bonded structural elements.

Animals↗

Use of reversed-phase and ion-exchange batch extraction in the purification of bovine pituitary peptides.

Bovine posterior pituitaries were extracted with an acidic medium designed to maximize solubilization of peptides while precipitating high-molecular-weight protein. The supernatant was then extracted with C18 reversed-phase cartridges to generate a peptide-enriched fraction. Cartridge eluates were subjected to ion-exchange extraction, using a batch procedure which fractionated the peptides into basic, acidic, and neutral pools. Amino-terminal fragments of bovine pro-opiomelanocortin were found to be resolved into separate pools by this method. The 1 to 49 fragment was eluted in the acidic pool while the 1 to 77 fragment was eluted in the basic pool. The 1 to 77 fragment was purified by reversed-phase high-performance liquid chromatography. Amino acid analysis of the fragments, generated from trypsin and V8 protease digestion of the 1 to 77 fragment, permitted assignment of cystine bridges between residues 2 and 24 and between residues 8 and 20. Results from amino sugar analysis were consistent with the presence of an O-linked oligosaccharide at threonine45 and an N-linked oligosaccharide at asparagine65.

Amino Acid Sequence↗

The respiratory burst is not required for killing of intracellular and extracellular parasites by a lymphokine-activated macrophage cell line.

The macrophage cell line, IC-21, was found to be incapable of producing the oxygen products associated with the respiratory burst. However, IC-21 cells were activated by lymphokine (LK) to kill intracellular (Leishmania donovani amastigotes) and extracellular (Schistosoma mansoni larvae) parasites, as well as tumor cells. In each case, the cytotoxicity exhibited by activated IC-21 cells and activated peritoneal macrophages was indistinguishable. However, nonactivated IC-21 cells were unable to kill L. donovani log-growth phase promastigotes, while nonactivated peritoneal macrophages destroyed greater than 90% of the initial infection. These results indicate that amastigotes and schistosome larvae are susceptible to killing by nonoxidative cytotoxic mechanism induced by lymphokine activation but, on the other hand, support the concept that the killing of log-growth phase promastigotes by nonactivated cells is dependent upon the respiratory burst. We propose that the IC-21 cell line may be a useful model for studying nonoxidative killing functions of activated macrophages.

Animals↗

Transferrin receptor induction is required for human B-lymphocyte activation but not for immunoglobulin secretion.

Transferrin receptors are expressed on proliferating cells and are required for their growth. Transferrin receptors can be detected after, but not before, mitogenic stimulation of normal peripheral blood T and B cells. In the experiments reported here we have examined the regulation of transferrin receptor expression on activated human B cells and whether or not these receptors are necessary for activation to occur. Activation was assessed by studying both proliferation and immunoglobulin secretion. We have determined that transferrin receptor expression on B cells is regulated by a factor contained in supernatants of mitogen-stimulated T cells (probably B-cell growth factor). This expression is required for proliferation to occur, since antibody to transferrin receptor (42/6) blocks B-cell proliferation. Induction of immunoglobulin secretion, however, although dependent on PHA-treated T-cell supernatant, is not dependent on transferrin receptor expression and can occur in mitogen-stimulated cells whose proliferation has been blocked by antitransferrin receptor antibody. In addition, we have demonstrated that IgM messenger RNA induction following mitogen stimulation is unaffected by antitransferrin receptor antibody. These findings support a model for B-cell activation in which mitogen (or antigen) delivers two concurrent but distinct signals to B cells: one, dependent on B-cell growth factor and transferrin receptor expression, for proliferation, and a second, dependent on T cell-derived factors and not requiring transferrin receptors, which leads to immunoglobulin secretion.

Antibodies, Monoclonal↗

Effect of different growth hormone-releasing factors on the concentrations of growth hormone, insulin and metabolites in the plasma of sheep maintained in positive and negative energy balance.

Three experiments were conducted to compare the ability of different preparations of growth hormone-releasing factor (GRF) to stimulate GH secretion in sheep maintained in positive and negative energy balance. In experiment 1 five sheep were injected (i.v.) with three preparations of human pancreatic GRF (hpGRF-44, hpGRF-40, hpGRF-29-NH2) and one preparation of rat hypothalamic GRF (rhGRF-29-NH2) all at 98.0 pmol/kg, or control vehicle, in a Latin square design when the animals either had free access to food or were fed half their maintenance requirements. Analysis of plasma samples, obtained before and for 150 min after injection, revealed that the reduced food intake resulted in the expected changes in body weight and circulating GH, insulin, glucose, urea and non-esterified fatty acids. The maximum post-injection concentrations of GH did not differ between either the two levels of feeding or the four GRF preparations but the mean post-injection concentration of GH was significantly higher for all GRF treatments on the restricted ration (P less than 0.001). The mean post-injection response to rhGRF-29-NH2 was less than that obtained with hpGRF-44 for sheep with food available ad libitum (P less than 0.05) and was clearly more persistent for all GRF treatments in animals fed the reduced diet (P less than 0.001). In experiment 2 the same five sheep were injected i.v. with rhGRF-29-NH2 (98.0 pmol/kg) when they had free access to food and after food had been withdrawn for 3 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effect of intravenous bovine growth hormone or human pancreatic growth hormone-releasing factor on milk production and plasma hormones and metabolites in sheep.

Although it is well known that exogenous bovine GH (bGH) increases milk yield in ruminants it has not been possible to determine whether an increase in endogenous GH secretion has the same effect. The recent isolation of human pancreatic GH-releasing factor (hpGRF-44) has enabled this comparison of the effects of bGH and hpGRF-44 on milk production in sheep. Three pairs of Dorset ewes underwent three 4-day treatments according to a Latin square design. Treatment 1 involved: 2-hourly i.v. injections (approximately 3.0 ml) of bGH (15 micrograms/kg; 1.8 units/mg); treatment 2: 2-hourly i.v. injections (approximately 3.0 ml) of hpGRF-44 (0.6 microgram/kg); treatment 3: 2-hourly i.v. injections (3.0 ml) of the vehicle. Treatment periods were separated by 10 days. Sheep were milked twice daily and the milk was analysed for fat, protein and lactose. Blood samples (5.0 ml) were taken before and at 15, 45, 75 and 100 min after every third injection throughout the 4 days. Plasma was analysed for insulin, glucose, urea and non-esterified fatty acids (NEFA). The changes in plasma GH stimulated by hpGRF-44 were consistent and repeatable throughout the 4 days of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The decreasing incidence of pneumothorax and improving survival of infants with congenital diaphragmatic hernia.

In the 6-year period between 1977 and 1982 inclusive, 75 newborn infants with congenital diaphragmatic hernia of Bochdelek underwent corrective surgery during the first 24 hours of life. A total of 40 infants (53%) survived. Beginning in January 1980, a standardized approach to care including early use of mechanical ventilation and paralysis with pancuronium as well as dopamine use prior to any Priscoline infusion, was instituted. To determine whether these approaches improved outcome, term infants without malformations from the years 1977 to 1979 were compared with a similar group treated after institution of standardized care between 1980 and 1982 inclusive. The infants were comparable in all respects, but survival improved from 45% to 82% between the two periods (P less than 0.03). There was an associated decrease in the incidence of pneumothorax (45% in first period; 14% in second period) paralleled by a concomitant increase in pancuronium use (18% and 85%, respectively). Although factors responsible for the improved survival are multifactorial these data indicate the detrimental effect of pneumothorax on outcome and the beneficial effect of a standardized approach to care using conventional intensive care techniques.

Critical Care↗

Total parenteral nutrition in pancreatic disease.

Total parenteral nutrition (TPN) was given to 121 patients admitted with severe pancreatitis (73), chronic pancreatitis (23), or pancreatic malignancy (25) over 104 months. No adverse effects on the pancreas were detected from the TPN, including the provision of intravenous (IV) fat. Nutritional status was maintained or improved in all groups, including patients undergoing surgical procedures and those experiencing marked stress. No significant impact on the clinical course of pancreatitis was observed, although the death rate in acute pancreatitis (15.2%) and complicated pancreatitis (18.5%) compares favorably with other published series where early surgical intervention was undertaken. There was an increased risk of catheter-related sepsis in patients with complicated pancreatitis (14.8%) and with chronic pancreatitis (17.4%). No increase septic risk was seen in patients with acute pancreatitis or pancreatic malignancy. Eighty-two per cent of patients with acute pancreatitis required an average of 87 units of insulin per day while 78% of patients with chronic pancreatitis required an average of 54 units per day. In summary, TPN proved to be safe, effective, and well-tolerated in those patients with disorders of the pancreas.

Adolescent↗

Mechanisms of protective immunity against S. mansoni infection in mice vaccinated with irradiated cercariae. VI. Influence of the major histocompatibility complex.

Inbred mouse strains develop different levels of resistance to challenge infection with Schistosoma mansoni in response to vaccination with irradiated cercariae. The role of the major histocompatibility complex (MHC) in determining this genetic polymorphism in acquired resistance was investigated. Previous studies suggested that inbred mice bearing either the b or d MHC haplotypes develop a higher level of vaccine induced resistance than do mice with other MHC haplotypes. An analysis of an F1 cross between an H-2b strain (C57BL/6) and an H-2k strain (C3H/HeJ) indicated that the ability to develop high levels of immunity is inherited in a dominant fashion. In order to confirm that the development of high resistance is an MHC associated trait, B10, C3H, BALB and B6 congenic mice bearing different H-2 haplotypes were compared. On either the B10, B6, or BALB background, substitution of b or d with k or a MHC alleles resulted in a decreased level of vaccine induced immunity. The observed decreases were more pronounced in BALB and B6 than in B10 congenics suggesting an influence of background (non-MHC linked) genes on protective immunity. Similarly, C3H.SW (H-2b) mice developed a significantly higher level of acquired resistance than C3H/HeSn (H-2k) mice. Cross and backcross experiments between H-2b and H-2k B6 congenic mice confirmed the dominant inheritance of high resistance as well as the MHC linkage of the trait. These data indicate that the MHC locus exerts a quantitative influence on vaccine induced resistance in certain inbred mouse strains and provide further support for the concept that the protection elicited by irradiated cercariae is the manifestation of a specific host immune response.

Alleles↗

Effect of intravenous administration of growth hormone-releasing factor (hpGRF-44) and Tyr-D-Trp-Ala-Trp-D-Phe-NH2 on plasma hormones and metabolites in goats.

It has recently been demonstrated that human pancreatic GH-releasing factor (hpGRF-44) and Tyr-D-Trp-Ala-Trp-D-Phe-NH2 (subsequently referred to as 'the peptide') release GH from rat pituitary glands maintained in vitro and, in the former case, increase circulating GH in rats and man. The commercial importance of discovering an agent capable of specifically enhancing GH secretion in ruminants stimulated the present study which examined: the intravenous administration of both peptides on plasma GH, prolactin, insulin, glucose, urea and non-esterified fatty acids in goats and the effect of the peptide on the release of GH from sheep pituitary glands maintained in vitro. The peptide was injected into the jugular vein of goats in three different forms and at several concentrations (dispersal by shaking, 0.07 microgram/kg; 0.7 microgram/kg; ball-milled, 7.0 micrograms/kg, 70 micrograms/kg; dimethyl sulphoxide (5%), 7.0 micrograms/kg, 70 micrograms/kg). None of the treatments stimulated a significant increase in circulating GH. Nevertheless the peptide (20 micrograms/ml medium) was found to stimulate a 50-60% increase in the production of GH from sheep pituitary glands maintained in vitro. The effect of intravenously injecting hpGRF-44 (1.0 microgram/kg) was investigated in the present and absence of passive immunization with sheep anti-somatostatin immunoglobulin G (IgG) (a bolus of 600 mg, 3 h before treatment with hpGRF-44). Plasma GH was increased (P less than 0.001) within 15 min of treatment and the magnitude of the response was the same for both the immunized and non-immunized goats. A second peak was measured after approximately 75 min which was only significant (P less than 0.05) in the immunized group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Maternal depression in an urban pediatric practice: implications for health care delivery.

A scale to measure depressive symptomatology was administered to mothers attending an urban pediatric primary care center. Over 50 per cent of the female heads of households were Black or low income and depressed. This suggests that the provider of pediatric primary care should recognize depression and make appropriate referrals or intervention, since depressed mothers may have a diminished ability to respond to the emotional needs of their children.

Adolescent↗

Autologous marrow transplantation after karyotypic conversion to normal in blastic phase of chronic myelocytic leukemia.

A patient with blastic transformation of Philadelphia chromosome-positive chronic myelocytic leukemia was treated with acridinyl anisidide, which resulted in conversion to a normal karyotype. At that time, bone marrow was harvested and cryopreserved. After relapse, the patient was treated with cyclophosphamide and fractionated total body irradiation followed by autologous marrow transplantation. Serial karyotypes and blood counts, determined up to 14 months after transplantation, remained normal.

Bone Marrow Transplantation↗

Development and application of a radioimmunoassay for pepleomycin.

A rapid sensitive radioimmunoassay for pepleomycin (PM) has been developed using an antiserum produced in a sheep in response to a bovine serum albumin-drug conjugate. Radioiodinated PM was prepared using Iodogen. The assay was reproducible with a limit of detection in plasma of 200 ng/liter. The antiserum does not cross-react with bleomycin or with a number of unrelated drugs. Pharmacokinetic studies using the assay were carried out in three patients who received a short iv infusion of 5 mg/m2 of PM. The drug disappeared from the plasma with an elimination half-life of approximately 3 hours.

Animals↗

Lafora disease: diagnosis by liver biopsy.

We have studied four patients who had a clinical course compatible with Lafora disease. The diagnosis was confirmed in one by the presence of Lafora bodies in central nervous system neurons at autopsy and was supported in another by findings in the cerebral biopsy of a sibling. Our patients had no clinically apparent liver disease, but liver specimens in each instance showed a distinctive histological abnormality, with hepatocytes containing inclusions having a ground-glass appearance. The liver biopsy findings appear to be relatively specific for this disorder and can easily be differentiated from those in other liver diseases.

Adolescent↗

Thiamine uptake in isolated schizonts of Eimeria tenella and the inhibitory effects of amprolium.

The uptake of thiamine by isolated second-generation schizonts of Eimeria tenella and by host intestinal cells was found to consist of two components. One was passive and the other apparently an active process. The kinetic constants of the latter were compared in host (Km = 0.36 microM) and parasite (Km = 0.07 microM) and found to be significantly different. Both systems were competitively inhibited by amprolium but showed different affinities for the drug. (Host Ki = 323 microM; parasite Ki = 7.6 microM). Further differences were observed in schizonts of a drug-resistant line of E. tenella. These findings are discussed in terms of the inhibition of thiamine uptake being the basis of the anticoccidial activity of amprolium.

Amprolium↗