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Biomedical subjects

S Adams

Publications and source records attributed to S Adams.

At least 109 records · Page 6Linked to original sources
PubMed1995

Immunization with a soluble recombinant HIV protein entrapped in biodegradable microparticles induces HIV-specific CD8+ cytotoxic T lymphocytes and CD4+ Th1 cells.

One of the major obstacles to the development of successful recombinant vaccines against human immunodeficiency virus (HIV) and other intracellular pathogens is the identification of a safe and effective vaccine delivery system for the induction of cell mediated immunity with soluble protein antigens. In this study it was demonstrated that immunization with a recombinant HIV envelop (env) protein entrapped in biodegradable poly(lactide-co-glycolide) (PLG) microparticles induced consistent HIV-specific CD4+ and CD8+ T-cell responses in mice. Major histocompatibility complex (MHC) class I-restricted cytotoxic T lymphocytes (CTL) responses were detected following a single systemic immunization with gp120 entrapped microparticles and when given by the intranasal (i.n.) route induced HIV-specific CD8+ CTL and secretory IgA. Furthermore immunization with gp120 entrapped in microparticles generated CD4+ T cells that secreted moderate to high levels of IFN-gamma. Therefore, PLG microparticles are a safe and effective means of delivering antigen to the appropriate processing site for the generation of class I-restricted CTL, and are also capable of inducing Th1 cells.

Animals↗
PubMed1995

Pharmacokinetics and bioavailability of rhIGF-I/IGFBP-3 in the rat and monkey.

Circulating IGF-I exists primarily as part of a ternary 150 kDa complex comprising equimolar amounts of IGF-I, IGFBP-3 and acid labile subunit (ALS). It is also known that in contrast to IGF-I and IGFBP-3 there exists a substantial quantity of unbound ALS in the circulation. As part of our preclinical development program, we have investigated the pharmacokinetic properties of a complex of human recombinant IGF-I and IGFBP-3. Systematic administration of rhIGF-I/IGFBP-3 results in binding of this binary complex to endogenous free ALS and thus leads to increased circulating levels of 150 kD ternary complex (IGF-I/IGFBP-3/ALS). In contrast to the administration of free IGF-I, IGF-I/IGFBP-3 dosing leads to increased systemic IGF-I exposure (i.e. increased area under the time vs. serum concentration curve or AUC) and decreased clearance (CL). Upon administration of equimolar doses of IGF-I/IGFBP-3 to the rat and monkey, it was found that in the monkey AUC was increased and CL decreased when compared to the rat. In addition, the pharmacokinetic profile suggests that saturation of excess ALS occurs at considerably lower doses of rhIGF-I/IGFBP-3 in the monkey than in the rat. Finally, the bioavailability of rhIGF-I/IGFBP-3 was assessed in the rat and found to be approximately 85% and 50% after intramuscular and sub-cutaneous administration, respectively. It was concluded that the formation of the 150 kD ternary complex had a significant impact on increasing the systemic exposure to rhIGF-I when administered as the binary complex (rhIGF-I/IGFBP-3). In addition, IGFBP-3 increases the therapeutic index of rhIGF-I even at doses that significantly exceed the saturation of ALS.

Animals↗
PubMed1995

Systemic administration of rhIGF-I or rhIGF-I/IGFBP-3 increases cortical bone and lean body mass in ovariectomized rats.

The purpose of this study was to compare dose-related effects on cortical bone and lean body mass following subcutaneous administration of rhIGF-I alone, or bound to an equimolar amount of rhIGFBP-3 to adult Ovx rats. At the age of 16 weeks, rats were ovariectomized or sham-operated and were allowed 8 weeks to develop osteopenia. After being divided into control (saline treated) or treatment groups, rats were injected daily during an 8-week period with 0.9 and 2.6 mg/kg of rhIGF-I, or with 0.9, 2.6, and 7.5 mg/kg of rhIGF-I bound to rhIGFBP-3. Fluorescent bone markers were given 9 and 2 days prior to necropsy. Body weights and lean body mass were monitored throughout the experiment. Cortical bone histomorphometry was performed on tibial cross-sections at the tibiofibular junction, and endochondral bone growth was measured at the distal femoral metaphysis. All rats treated with rhIGF-I or the rhIGF-I/IGFBP-3 complex had increased body weights, corresponding to a dose-dependent increase in lean body mass. Endochondral growth was slightly increased in all experimental groups, but was not dose-dependent. A dramatic increase in periosteal, modeling-dependent formation, coupled with decreased or unchanged resorption on the endocortical envelope resulted in a dose-dependent increase in cortical thickness and cross-sectional area in groups treated with the complex of rhIGF-I/IGFBP-3. This complex appeared to be more effective in promoting positive musculoskeletal changes than rhIGF-I alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗
PubMed1995

De novo development and self-replenishment of B cells.

Previous studies distinguished two murine B cell lineages: the conventional lineage, which comprises the majority of B cells, and the Ly-1 B lineage (B-1a), which represents a small percentage of total adult B cells. A third subset, B-1b cells, shares many properties with B-1a cells, including the characteristic ability to self-replenish, but does not express Ly-1 (CD5). Reconstitution studies presented here show that (i) although the B220- population in adult spleen and bone marrow contains very little progenitor activity for B-1a cells, it can reconstitute roughly half the normal number of B-1b cells; (ii) B-1 progenitors present in adult bone marrow and spleen function at low levels in adult animals; (iii) peritoneal B-1 cells (principally B-1b) that develop following bone marrow transfer, like B-1 cells from normal animals, are capable of substantial self-replenishment; and (iv) conventional B cells do not expand (self-replenish) in adoptive recipients, although they can persist for long periods. Collectively, these progenitor and self-replenishment characteristics provide a developmental base for distinguishing B-1a, B-1b and conventional B cells.

Age Factors↗
PubMed1995

Interleukin-1 expression by neutrophils in rheumatoid arthritis.

OBJECTIVE: To determine if neutrophils from blood and synovial fluid of patients with rheumatoid arthritis and other joint arthropathies express interleukin-1 beta mRNA. METHODS: RNA was isolated from neutrophils from patient and control blood, and synovial fluid of patients, probed in northern blots, and quantified by densitometry. It was also isolated and analysed from control blood neutrophils after incubation in vitro with granulocyte macrophage colony stimulating factor (GM-CSF). RESULTS: Neutrophils from the synovial fluid of patients with rheumatoid arthritis contained low levels of mRNA for interleukin-1 beta--between 0.1 and 2% of those observed during stimulation of control neutrophils with GM-CSF for one hour. Higher levels (4-40% of the maximal GM-CSF values) were observed in blood neutrophils from patients with rheumatoid arthritis. CONCLUSIONS: Neutrophils contribute to the cytokine network in rheumatoid arthritis. In some circumstances, activation of transcription may occur within the circulation of these patients.

Arthritis, Rheumatoid↗
PubMed1995

Adrenocortical and behavioral predictors of immune responses to starting school.

Associations between major psychologic stressors and immune function have been documented in previous research, but few studies have investigated immune changes attending minor, normative stressors. This study examined adrenocortical and behavioral predictors of immune responses to starting kindergarten in 39 five-year-old children, who completed laboratory visits for venipunctures 1 wk before (time 1) and 1 wk after (time 2) school entry. At time 1, children were also immunized with pneumococcal vaccine. Immune responses were measured as change scores for T (CD4+ and CD8+) cells, B (CD19+) cells, lymphoproliferative responses to pokeweed mitogen (PWM), and type-specific pneumococcal antibody responses (ABR). Adrenocortical response was assessed as the change in salivary cortisol level, and behavioral difficulty with school adjustment was scored using parental ratings of behavior problems, stress due to changes in routines, and degree of adaptive challenge. Salivary cortisol rose after kindergarten entry (means = 0.39 +/- 0.28 to 0.49 +/- 0.36 micrograms/dL, p = 0.03) and was unrelated to behavioral difficulties. CD4+ cells increased in number, whereas PWM declined, and CD19+ cells showed a borderline increase. Change in salivary cortisol was positively associated with change in CD19+ (delta CD19+) and inversely related to ABR. Scores for behavioral difficulty were inversely associated with delta CD4+ and delta CD19+. These data suggest that: 1) school entry is a stressor capable of evoking elevations in cortisol and behavior problems, accompanied by shifts in functional and enumerative measures of immune status; and 2) children with greater adrenocortical reactivity have increases in B cell numbers and less effective B cell-mediated antibody production, whereas children with more behavioral difficulties show declines in all T and B cell subsets.

Adrenal Cortex↗
PubMed1995

Effects of methylphenidate in HIV-related depression: a comparative trial with desipramine.

This report is a randomized, double-blind, comparative trial of desipramine with the psychomotor stimulant methylphenidate. Twenty HIV antibody-positive patients with depressive symptoms were randomly assigned to either drug. After individual dose titration, the mean daily dose of desipramine was 150 mg. and methylphenidate 30 mg. daily. The differences in responses between desipramine and methylphenidate were not statistically significant on various measures of depression. The antidepressant effect of methylphenidate did not occur any faster than that of desipramine. Both significantly reduced depressive and anxious symptomatology over the blinded portion of the treatments. Thus, methylphenidate relieves depressive symptomatology with efficacy similar to that of desipramine, offering an alternative to patients who are unable to tolerate standard tricyclic antidepressant therapy. The dopaminergic effects of methylphenidate are likely to mediate its antidepressant effects.

Adult↗
PubMed1995

Induction of IgA and IgG antibodies in vaginal fluid, serum and saliva following immunization of genital and gut associated lymphoid tissue.

Vaginal immunization with the Simian immunodeficiency virus (SIV) was investigated in macaques in order to study genital mucosal antibodies. A combined route of genital- and gut-associated lymphoid tissues was used to stimulate IgA and IgG antibodies in vaginal fluid, serum and saliva. Macaques were immunized with a recombinant, particulate SIV antigen (SIV gag P27), covalently linked to the mucosal adjuvant cholera toxin B subunit (CTB). The animals were immunized sequentially as follows: vaginal (x2) followed by oral (x3), or the reverse sequence of immunization. The results show that both vaginal followed by oral immunization or the reverse sequence induces specific p27 IgA and IgG antibodies in the vaginal fluid and serum. IgA antibodies were also detected in saliva. Vaginal IgA antibodies have the secretory component and J chain suggesting that they are of secretory origin.

Adjuvants, Immunologic↗
PubMed1995

Surface morphology and chemical characterization of abrasion/erosion lesions.

PURPOSE: To describe the dentin surface morphology of abrasion/erosion lesions and to chemically characterize in vivo samples of sclerotic dentin. MATERIALS AND METHODS: Baseline polyvinylsiloxane impressions of eight in vivo caries-free lesions were taken. Dentin was collected from retention grooves for FTIR photoacoustic spectroscopic analysis. The cavity preparation was etched for 30 seconds with 37% phosphoric acid, rinsed, and dried. Impressions were taken of the etched surfaces. Epoxy resin dies were made of baseline and etched impressions, sputter-coated and examined at x1000 with the SEM. RESULTS: Lateral dentin tubule orientation was observed at gingival margins and on occlusal walls. Open cross-sectional tubules were seen at the depth of the groove. The mineral/protein ratio in the FTIR/PAS spectra of in vivo unetched sclerotic dentin samples suggested an increased mineral content.

Acid Etching, Dental↗
PubMed1995

HLA-DQ1 is associated with clinical response and survival of patients with melanoma who are treated with interleukin-2.

AIM: The risk of developing melanoma, the natural history of this disease, and the response to therapy with biological reagents may be determined, in part, by a patient's human leukocyte antigen (HLA) phenotype. In order to study this, the relationship between HLA type and clinical response to therapy with interleukin-2 (IL-2) was evaluated. METHODS: We retrospectively determined the HLA phenotype of 82 patients with metastatic melanoma who were treated with IL-2-based therapy. Fresh or frozen lymphocytes were serologically typed by standard lymphocytotoxicity techniques (NIH or Amos modified). The treatment regimens included IL-2 alone or with tumour infiltrating lymphocytes, lymphokine activated killer cells, cyclophosphamide, interferon-alpha, and tumour necrosis factor-alpha. Initially, the relationship between clinical response and each HLA antigen was evaluated by performing a two-tailed Fisher exact test. Associations with a P-value less than or equal to 0.10 without adjustment for multiple comparisons were considered worthy of further study. Independent confirmation of these apparent associations was obtained by studying the relationship between HLA phenotype and patient survival using Cox proportional hazards models. RESULTS: In the initial screening, a statistically significant association between clinical response and the expression of HLA-DQ1 was observed (unadjusted P2 = 0.0017). HLA-DQ1 was also independently associated with prolonged survival (P2 = 0.026). This positive association with survival was evident both for patients who responded to therapy and those who did not respond, as defined by > 50% tumour regression. CONCLUSIONS: Among patients with metastatic melanoma, HLA-DQ1 appears to be associated with clinical response to therapy using IL-2. This apparent association is confirmed by the observation that HLA-DQ1 is independently associated with prolonged survival in this group of patients.

Alleles↗
PubMed1995

[Intraoperative localization of metastases with a hand-held gamma probe].

A 50-y-old male patient with prostate cancer showed two suspicious lesions in bone scintigrams. They were assessed to be bone metastases by biopsy of the os ilium. After i.v. injection of 99mTc-HMDP a probe-guided localization permitted optimal surgical treatment. A bone metastasis in the os ilium was confirmed. The intraoperative detection with a hand-held gamma probe permitted accurate and complete excision of the tumour; the bone defect could thus be reduced to a minimum.

Bone Neoplasms↗
PubMed1994

Immunoscintigraphy of human mammary carcinoma xenografts using monoclonal antibodies 12H12 and BM-2 labeled with 99mTc and radioiodine.

For immunoscintigraphic localization of human breast cancer two monoclonal antibodies (mabs) 12H12 (immunoglobulin G1) and BM-2 (immunoglobulin G3) were developed. The mabs, directed against two different epitopes on the mucin glycoprotein TAG-12, showed reactivity with 96% of all primary mammary carcinomas. The antibodies were labeled with either 125I or 131I. In addition, 12H12 was directly labeled with 99mTc according to the method of Schwarz and Steinsträsser (A. Schwarz and A. Steinsträsser, J. Nucl. Med., 28:721, 1987). Biodistribution was measured in female nude mice bearing the human mammary carcinoma SF-15. Both radioiodinated mabs showed similar biodistribution with fast tumor uptake (8.5% injected dose/g at 6 h postinjection), which increased to 10-11% injected dose/g at 24 h and subsequently remained constant up to 120 h. 99mTc-Labeling of the mab 12H12 led to an enhanced tumor uptake of 10.5 and 14% injected dose/g at 6 and 24 h postinjection, respectively, and to significantly accelerated blood clearance of radioactivity. Similar results were obtained with a second mammary tumor (AR-1), while an endometrial tumor (EK-3) showed a 3-fold lower accumulation of radioactivity and no difference in uptake of radio-iodinated and 99mTc-labeled 12H12. Scintigraphic imaging of tumor-bearing nude mice with the 99mTc 12H12 at 24 h postinjection clearly demonstrated a diagnostic potential of the new mab for tumor localization and staging.

Animals↗
PubMed1994

Initial clinical results with technetium-99m-labeled LL2 monoclonal antibody fragment in the radioimmunodetection of B-cell lymphomas.

BACKGROUND: Various monoclonal antibodies (MoAb) labeled with Iodine-131 or Indium-111 (In-111) have been investigated for radioimmunodetection of Hodgkin's and non-Hodgkin's lymphomas. Successful radioimmunotherapy also has been reported. The purpose of this pilot study was to stage non-Hodgkin's B-cell lymphomas (NHL) using whole body scintigraphy with technetium-99m (Tc-99m)-labeled murine monoclonal antibody LL2 (EPB-2) Fab' (Immunomedics, Morris Plains, NJ). Others have shown this MoAb to have specific binding to B-cell lymphomas by flow cytometry and immunofluorescence. Initial clinical studies by others have demonstrated targeting of NHL with the Tc-99m-labeled LL2-Fab'. METHODS: One milligram of the antibody was injected intravenously after being radiolabeled with 30 mCi Tc-99m. Fifteen patients with high (n = 6), low (n = 2), and intermediate (n = 7) grade NHL were studied. No adverse effects were noted. Planar whole body imaging and single-photon emission computed tomography were performed at 2-6 h and 20-24 h postinjection. Human anti-mouse antibody levels were determined before injection and at 2 and 6 weeks. RESULTS: In 4 of 15 patients (27%), the disease stage was altered in response to the scintigraphic findings. The physiologic biodistribution of the antibody demonstrated splenic uptake caused by antibody targeting of the white pulp and of normal B-cells, and renal uptake caused by urinary excretion. Lymph node and bone marrow involvement of known tumor sites were clearly seen. A number of previously unknown tumor sites were revealed by LL2-radioimmunodetection despite normal morphologic imaging results. Long-term follow-up of these patients is required to verify these findings. No human anti-mouse antibody elevations or adverse reactions were found in the patients studied. CONCLUSION: These preliminary data suggest that Tc-99m-labeled LL2 Fab' yields useful clinical results, especially for the staging of patients with NHL before initial therapy or for the detection of early disease recurrence.

Animals↗