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Biomedical subjects

S A Anderson

Publications and source records attributed to S A Anderson.

At least 19 recordsLinked to original sources

Adjuvanticity of stearyl tyrosine on the antibody response to peptide 503-535 from HIV gp160.

In this present report we compare the humoral immune response induced by immunization with an HIV-1 gp160 peptide corresponding to amino acid sequence 503-535 complexed with different adjuvants. Specifically, the antipeptide, anti-HIV-1 gp160 and neutralizing antibody responses were measured in groups of mice and baboons that received peptide 503-535 conjugated to a carrier protein in either saline, alum, or stearyl tyrosine. The highest antibody responses were induced when mice and baboons were immunized with peptide adsorbed on stearyl tyrosine. These data indicate that stearyl tyrosine represents a potent candidate as a nontoxic adjuvant not only for subunit viral vaccines, but also for HIV peptides.

Adjuvants, Immunologic

Characterization of private and cross-reactive idiotypes associated with human antibodies to hepatitis B surface antigen.

Four mouse monoclonal anti-idiotypic antibodies (anti-Id) were generated against human monoclonal and polyclonal antibodies to hepatitis B surface antigen (HBsAg). These monoclonal anti-Id, along with a polyclonal anti-Id raised in rabbits, were used to characterize the idiotype (Id) specificity of the human antibody response to HBsAg (anti-HBs). The anti-Id reagents identified distinct private and cross-reactive Id expressed on monoclonal and polyclonal human anti-HBs preparations respectively. The anti-Id recognized both HBsAg combining site and non-combining site related private Id, and HBsAg combining site related cross-reactive Id. The Id specificities recognized by two of the monoclonal anti-Id were associated with the H chain alone, whereas two of the monoclonal anti-Id, along with the polyclonal anti-Id appeared to recognize Id determinants associated with both isolated H and L chains. These data suggest that Id heterogeneity exists within the human antibody response to HBsAg. The knowledge that Id heterogeneity exists is of importance in understanding the observed variability in the immune response during hepatitis B virus infection.

Antibody Specificity

Comparison of antibody reactivity to human immunodeficiency virus type 1 (HIV-1) gp160 epitopes in sera from HIV-1-infected individuals from Tanzania and from the United States.

In this study, we compared sera from 159 human immunodeficiency virus type 1 (HIV-1)-infected individuals from Tanzania and 103 infected individuals from the United States for antibodies reactive with 10 HIV-1 gp160 epitopes defined by synthetic peptides. Our data indicate that the anti-gp160 antibody fine specificity differs between infected individuals from these two geographically diverse populations. For example, 50% of the Tanzanian sera contained antibodies reactive with an immunodominant HIV-1 gp41 epitope defined by peptide 600-611, whereas 91% of the sera from the United States were reactive. Differences in serologic reactivity between HIV-1-infected individuals from Tanzania and the United States were also observed with gp160 epitopes defined by peptides 503-528 and 846-860. Included among the peptides examined were four which corresponded to the V3 region of gp120. The majority of sera from either country contained antibodies reactive with peptide RP142, whose V3 sequence is based upon that of HIV-1 isolate MN. Further characterization of serologic reactivity suggested that sera from Tanzania were more likely to neutralize HIV-1 isolate IIIB or MN in vitro than were sera from the United States. These differences in antibody fine specificity between HIV-1-infected individuals from Tanzania and the United States suggest that regional isolates of HIV-1 may exist.

Acquired Immunodeficiency Syndrome

Examination of sera from human immunodeficiency virus type 1 (HIV-1)-infected individuals for antibodies reactive with peptides corresponding to the principal neutralizing determinant of HIV-1 gp120 and for in vitro neutralizing activity.

Sera from human immunodeficiency virus type 1 (HIV-1)-infected individuals from the United States and Tanzania were examined for antibody reactivity to four synthetic peptides which corresponded to the principal neutralizing determinant from the V3 region of HIV-1 gp120. We observed that the majority of sera from both countries contained antibodies reactive with a V3 peptide whose sequence is based on that of the HIV-1 MN isolate. We were unable to establish a relationship between the presence of V3-reactive antibodies, as measured by enzyme-linked immunosorbent assay and neutralization of homologous HIV-1 isolates, in sera from either the United States or Tanzania. We observed that some sera which contained high antibody titers to the V3 peptides failed to neutralize HIV-1, while others with no antibody reactivity to the panel of V3 peptides exhibited in vitro neutralizing activity. These results suggest that neutralizing epitopes exist outside the V3 loop and that the presence of V3-reactive antibodies in sera does not imply in vitro neutralization of the homologous HIV-1 isolate. In addition, it appears that the V3 loop may consist of both neutralizing and nonneutralizing epitopes. The identification of neutralizing as well as nonneutralizing epitopes will be important for the design of potential HIV-1 vaccines.

Amino Acid Sequence

Differential activation of intracellular effector by two isoforms of human neurokinin-1 receptor.

Two isoforms of the human neurokinin-1 receptor were cloned and characterized in heterologous expression systems of mammalian cell culture and Xenopus oocytes. The two isoforms differ only in the length of the encoded polypeptide. The peptide-binding properties of the long form of human neurokinin-1 receptor are consistent with those of the native neurokinin-1 receptor of mammalian tissues, where substance P is the most potent agonist. Peptide agonists elicit an oscillating current in Xenopus oocytes expressing the long form. In contrast, the short form of human neurokinin-1 receptor expressed in COS cells binds substance P with an apparent affinity at least 10-fold lower than that of the long form, and it elicits the electrophysiological response only weakly in Xenopus oocytes. These data suggest that the short form couples to a different effector system. Sequence analysis suggested that the two isoforms may arise from alternative pre-mRNA splicing. These results indicate that multiple forms of the human neurokinin-1 receptor exist and the differential activation of intracellular effector may be involved in generating the complex biological effects of substance P.

Amino Acid Sequence

Satanism among adolescents: empirical and clinical considerations.

This paper reviews the literature on adolescent involvement in satanism. Results from a pilot study are presented along with a case study to illustrate factors that may alert practitioners to adolescents who are susceptible to satanic influences. Interventions for dealing with this adolescent subpopulation are discussed.

Adolescent

A randomized comparison of two doses of human lymphoblastoid interferon-alpha in hairy cell leukemia. Wellcome HCL Study Group.

One hundred thirty-eight patients with hairy cell leukemia were randomized to receive either a dose of 2.0 megaunits (MU)/m2 or a 10-fold lower dose of 0.2 MU/m2 of a highly purified natural alpha-interferon, administered daily for 28 days followed by a three times a week schedule. Ninety-seven of these patients had previously undergone splenectomy, but otherwise none of the patients had received prior therapy for their leukemia. The two doses were comparable in their effect on improving the neutrophil and platelet count, whereas the higher dose had a greater beneficial effect on the hemoglobin level and a greater antileukemic effect on the marrow. Acute toxicity in the form of a flu-like syndrome, neurologic side effects, neutropenia, and the need for platelet transfusions was observed less frequently in the low-dose group, as was the chronic fatigue syndrome. No neutralizing antibody activity was seen in the sera from 61 patients examined. Because of its beneficial effect on the neutrophil and platelet count and a lower degree of toxicity (ie, a superior therapeutic/toxicity ratio), the low dose is recommended as initial therapy in patients with hairy cell leukemia. This therapy may be followed by dose escalation once clinical improvement is observed.

Adult

Anti-idiotypic antibody response to monoclonal anti-CD4 preparations in nonhuman primate species.

A series of mouse monoclonal anti-CD4 preparations was characterized for the ability to recognize overlapping epitopes on CD4 and to inhibit HIV/simian immunodeficiency virus (SIV) syncytium formation. Based on this characterization, mAb able to recognize CD4 epitopes overlapping the HIV binding site were selected and used to immunize nonhuman primates to elicit the production of specific anti-Id antibodies. Five baboons and five rhesus monkeys were immunized with either individual or a cocktail consisting of several monoclonal anti-CD4 preparations. All the nonhuman primates produced specific anti-Id that recognized either private or cross-reactive Id depending on the monoclonal anti-CD4 used to generate the anti-Id response. Inhibition assays were performed to ascertain the ability of: 1) soluble CD4 to inhibit the Id-anti-Id reaction and 2) the various anti-Id to inhibit the CD4-monoclonal anti-CD4 reaction. These studies demonstrated that some of the anti-Id recognized a cross-reactive Id that was associated with the Ag-combining site. In addition, some of the anti-Id weakly recognized SIV gp120 by Western blot analysis. These studies may be useful in designing experiments that may lead to a better understanding of the CD4-HIV gp120 interaction and to the production of Id and/or anti-Id reagents that might be used to manipulate this virus-receptor interaction.

Animals

Vinblastine fails to improve response of renal cancer to interferon alfa-n1: high response rate in patients with pulmonary metastases.

One hundred sixty-five patients were randomized to receive either interferon alfa-n1 (Wellferon; Burroughs Wellcome Co, Research Triangle Park, NC) alone or with vinblastine. An initial six-cycle induction treatment consisted of interferon given at daily doses of 3, 5, 20, 20, and 20 x 10(6) U/m2 every 2 weeks. Vinblastine at a dose of 10 mg/m2 (later decreased to 5 mg/m2) was given on day 1 of alternate cycles. Toxicities were generally well tolerated. The overall response rate was 10% with no significant difference between treatment arms. Survival was also not significantly different for the arms. A small subset of patients (16) with metastases only to the lungs had a high complete response (CR) and partial response (PR) rate of 44%. Responses were durable, and overall survival of this group was much better than that of the other patients.

Antineoplastic Combined Chemotherapy Protocols

Similarity between parents' and adolescents' levels of individuation.

Intergenerational theories of family functioning and therapy have sparked interest in empirical investigations that test intergenerational relationships. Of particular interest is whether one generation's level of functioning is similar to that of the next generation. This paper presents a test of difference scores that enables researchers to compare related and unrelated dyads, thus creating a comparison group when using only two generations. This procedure is contrasted with correlational findings in testing the hypothesis that adolescents will have a level of individuation similar to that of their parents.

Adolescent

Dietary branched-chain amino acids and protein selection by rats.

Consumption by rats of high protein diets is associated with elevated plasma and brain concentrations of branched-chain amino acids (BCAA). We examined the possibility that changes in BCAA concentrations in blood and brain might serve as modulators of protein consumption. After young rats had adjusted to selecting between a 10% or 25% casein diet and a 50% casein diet, a mixture of BCAA was included in the diet containing the lower amount of protein (10% + BCAA, 25% + BCAA). Supplementation of the 10% or 25% casein diets with BCAA and subsequent elevation of BCAA concentrations in plasma and brain were associated with increased selection of protein in rats given the 10% + BCAA/50% casein diet choice, but not in rats offered the 25% + BCAA/50% casein diets. When no alternative diet was available, addition of BCAA to a 15% casein diet depressed food intake, and rats given a choice between a 15% casein diet with or without added BCAA selected almost exclusively the diet without added BCAA. Although BCAA concentrations were high in plasma and brain in all experiments, concentrations of methionine, tyrosine, phenylalanine, tryptophan and histidine were low in brain in experiments in which rats altered their diet or protein selection after BCAA addition. High concentrations of BCAA in plasma and brain were not consistently associated with changes in protein selection.

Amino Acids

A test of the Olson Circumplex Model: examining its curvilinear assumption and the presence of extreme types.

The debate over the usefulness of different family models continues. Recent attention has been paid to comparisons between the Olson Circumplex Model and the Beavers Systems Model. The present study seeks to contribute evidence that bears directly upon one of the most fundamental points of controversy surrounding the Olson model--the linear versus curvilinear nature of the cohesion and adaptability dimensions. A further contribution is an examination of the actual occurrence of the Circumplex Model's extreme types in a clinical population.

Adaptation, Psychological

Guidelines for use of dietary intake data.

This article presents the guidelines from the report of the ad hoc Expert Panel on Guidelines for Use of Dietary Intake Data. The report was prepared under terms of a contract with the Life Sciences Research Office of the Federation of American Societies for Experimental Biology to provide the Food and Drug Administration with a working reference for evaluating dietary intake data. The guidelines represent the Expert Panel's conclusions on appropriate ways to interpret dietary data relating to (a) prevalence of consumption of particular levels of foods or food components, (b) comparisons of intake of different groups within the U.S. population, (c) time trends in consumption of foods or food components, and (d) relationships of intake of a food or food component to a given health outcome. The guidelines address general issues concerning dietary data collection and statistical concerns as well as specific issues important in interpretation of dietary data.

Data Collection

Peripheral neuropathy as a component of the neuroleptic malignant syndrome.

The neuroleptic malignant syndrome, an idiosyncratic reaction to antipsychotic medication, is defined by the tetrad of autonomic dysfunction, rigidity, fever, and altered mental status. Two patients in whom this syndrome developed acquired severe peripheral neuropathies during the course of their illness. This demyelinative polyneuropathy has not been reported previously as occurring in the neuroleptic malignant syndrome.

Adult

Clinical pharmacology of torasemide, a new loop diuretic.

Torasemide is a new loop diuretic that potentially may have renal tubular effects from both the blood and urinary sides of the nephron. We assessed its pharmacokinetics and pharmacodynamics in eight normal subjects administering intravenous doses of 5, 10, and 20 mg compared with 40 mg furosemide. We assessed the effect of probenecid on response to the 20 mg dose. A dose intermediate to the 10 and 20 mg doses appeared equally natriuretic to 40 mg furosemide. Although total clearance was the same with all doses (about 0.45 ml/min/kg), renal clearance and the fraction of unchanged drug appearing in the urine decreased with higher doses raising the question of saturable renal secretion. Urinary dose-response curves showed torasemide to be five times as potent as furosemide. Probenecid pretreatment decreased both urine volume (P = 0.0016) and sodium excretion (P = 0.0003), implying that delivery of drug to the urinary side of the nephron is the major determinant of response.

Adult

Effect of high-dose etodolac on renal function.

Previous studies from our laboratory have demonstrated transient effects on renal function by etodolac, 200 mg b.i.d. The current study assessed the effects of a larger dose of etodolac (500 mg b.i.d.) to explore the time course of its renal effects and to determine whether the transient effect would become more prolonged with a larger dose. We studied 10 normal subjects and nine patients with renal insufficiency, examining the effects of the first 500 mg dose of etodolac as well as 4 days of b.i.d. administration. In both groups, etodolac transiently decreased fractional excretions of sodium and chloride and urinary prostaglandin E2. In patients, etodolac also transiently decreased inulin and para-aminohippuric acid clearances and urinary 6-keto-prostaglandin F1 alpha. Chronic administration caused no changes in renal function in either group. In summary, in this relatively small group of patients, high-dose etodolac caused only transient, fully reversible effects on renal function, the cumulative effect of which was negligible.

6-Ketoprostaglandin F1 alpha

Reversible acute decrease in renal function by NSAIDs in cirrhosis.

The effects of sulindac were compared with those of ibuprofen or naproxen on creatinine clearance and urinary prostanoids in patients with severe alcoholic cirrhosis. Sulindac caused acute declines in all renal parameters in four of five patients. The effect occurred with serum concentrations of the active sulfide metabolite comparable to those in patients with no hepatic impairment. The patient who was not affected had less effects on urinary PGE2 and TxB2 and no effect on 6-keto PGF1 alpha. In this patient, dosing with ibuprofen caused pronounced declines in all urinary prostanoids and a decrease in creatinine clearance. Two other patients treated with ibuprofen and one treated with naproxen also suffered decrements in all parameters. In conclusion, sulindac had suppressant effects on renal prostanoids associated with declines in creatinine clearance in these patients with cirrhosis, indicating a need for similar cautions with its use as with other NSAIDs.

Acute Disease

Effects of nonsteroidal antiinflammatory drugs on renal function in patients with renal insufficiency and in cirrhotics.

We have assessed the effects of acute and chronic administration of etodolac, ketoprofen, and indomethacin on renal function in patients with mild to moderate chronic renal insufficiency (CRI). We studied 18 normal volunteers and 24 patients with CRI due to hypertension and/or diabetes mellitus with creatinine clearances between 19 and 83 mL/min/1.73 m2. Clearance studies were performed with the first dose of nonsteroidal antiinflammatory drug (NSAID) to compare acute effects of the agent with a no-drug control. Subjects then received the NSAID for three to five days and, on the last day of study, underwent another clearance study to assess the effects of a single dose of NSAID superimposed on chronic dosing. With each dose of each NSAID, inulin and paraaminohippurate (PAH) clearances and fractional excretion of NA+ decreased. However, the baseline control collections after chronic dosing did not differ from the no-drug control periods. Hence, the decline in renal function with each dose is transient, and no overall adverse effect on renal function occurred with chronic dosing. In five patients with cirrhosis, we assessed the renal sparing effects of sulindac. After equilibration on a fixed sodium intake, they received a 200-mg dose of sulindac. In one patient, no adverse effect occurred; the remaining patients suffered declines in creatinine clearance of 29%, 87%, 37%, and 37%, respectively. This effect was transient and returned to control values six to eight hours after sulindac administration. At the time of maximal depression of renal function, serum concentrations of sulindac sulfide were comparable to those in subjects with normal hepatic function.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetates