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Biomedical subjects

S Adams

Publications and source records attributed to S Adams.

At least 19 recordsLinked to original sources
PubMed1995

Altered target organ. A mechanism of postrecovery resistance to murine autoimmune oophoritis.

Experimental murine autoimmune oophoritis, a model of human premature ovarian failure, is induced by immunization with a peptide of the ZP3 glycoprotein from mouse zona pellucida (ZP3(330-340)) in CFA. The ovarian pathology is mediated by ZP3-specific, CD4+ T cells, and not by Abs. We now show that mice recovered from autoimmune oophoritis in 4 mo, as characterized by regression of ovarian inflammation. Recovery was associated with disease resistance upon rechallenge with ZP3(330-340) in CFA. Oophoritis resistance was not explicable by immunosuppressive effect of CFA priming, nor by suppression of pathogenic T cells. ZP3-specific, proliferative T cell response could be detected, and a ZP3-specific, IFN-gamma-producing pathogenic T cell line was derived readily from the recovered mice by in vitro stimulation with the ZP3(330-340) peptide. Moreover, recovered mice, when challenged with ZP3(330-340) in CFA, produced Abs of IgG class to the ZP3(330-340) peptide. Suppressor T cells are not readily demonstrable. Most importantly, oophoritis occurred in normal ovaries implanted under the renal capsule of the recovered mice. That oophoritis developed in the implanted ovaries, but spared the endogenous ovaries, further indicates that the latter is refractory to oophoritis. Disease resistance of the ovaries is not explicable by limitation of accessible target Ags. When mated, recovered mice were fertile and produced normal litters; and, as recipients of a ZP3-specific T cell line, their ovaries developed oophoritis. We conclude that altered local environment of the target organ following autoimmune disease recovery can contribute to the complex disease-resistant state.

Animals↗
PubMed1995

[Systemic infection due to group A Streptococcus pyogenes].

A 47-year-old woman developed oedematous swelling of the skin over the left hip and leg, with joint pains and reddening over joints of the hands and left ankle. 2 months before her son had had scarlet fever, following which the patient had two episodes of fever. Shortly before hospitalization she was treated with a glucocorticoid because a rheumatic disease had been suspected. On admission the blood sedimentation rate was 58/90, the white cell count was 15.100/microliters with left shift in the differential count. The swellings in arms and legs became abscesses which were incised. An abscess over the left buttock, diagnosed by 67-gallium whole-body scintigraphy, was also treated surgically. On the day of admission penicillin (10 mill. IU three times daily intravenously) and, from the 4th day onwards, gentamicin (80 mg three times daily intravenously) were administered. Histological examination of fascia and muscle biopsies revealed nonspecific inflammation without signs of malignancy, white blood culture grew group A Streptococcus pyogenes. 20 days after the surgical intervention the patient was discharged in full health. Necrotizing fasciitis caused by Streptococcus pyogenes has become more frequent in the last few years and has often been accompanied by severe systemic complications.

Fasciitis↗
PubMed1995

Invariant chain peptides enhancing or inhibiting the presentation of antigenic peptides by major histocompatibility complex class II molecules.

Two soluble invariant chain (Ii) peptides with overlapping sequences had contrasting effects on the presentation of antigenic peptides by murine Ad, Ak, Ed, and Ek major histocompatibility complex (MHC) class II molecules. Naturally produced class II-associated invariant chain peptides human (h)Ii81-104/murine (m)Ii80-103 inhibited antigen presentation on these MHC class II alleles in a manner consistent with competitive inhibition. The Ii-4 peptides hIi77-92/mIi76-91 enhanced presentation of antigenic peptides on I-E class II alleles by promoting the exchange of peptides at the cell surface. Treatment of antigen-presenting cells (APC) with Ii-4 before the addition of antigenic peptide greatly enhanced subsequent T cell responses, while treatment of APC with Ii-4 after antigenic peptide binding decreased subsequent T cell responses. The hIi81-104 and mIi80-103 peptides inhibited T cell responses in both types of assays. The binding of biotinylated antigenic peptide to MHC class II-transfected L cells, as measured by flow cytometry, was inhibited by mIi80-103 and enhanced by mIi-4. Segments of Ii fragments remaining associated with MHC class II, or released Ii peptides, appear to regulate the formation of stable antigenic peptide/MHC class II complexes either positively or negatively through interactions at or near the antigenic peptide binding site. These findings open a pathway for the design of novel therapeutics based on the structure and function of natural and rationally designed fragments of Ii.

Amino Acid Sequence↗
PubMed1995

Allelic imbalance on chromosome 1 in human breast cancer. I. Minisatellite and RFLP analysis.

In order to characterise the role of chromosome 1 more fully in breast cancer, polymorphic markers mapping along the length of the whole chromosome were used to assess a panel of 71 tumour-lymphocyte pairs for allelic imbalance. Complex patterns of alterations were established that are consistent with cytogenetic data in the literature. Deletion mapping of individuals with loss of heterozygosity identified five independent smallest common regions of deletion, two of which are novel. There are also three discrete regions showing a gain in copy number of one homologue. The two arms of the chromosome may be subject to different events; the short arm primarily undergoes interstitial deletions, whereas the long arm is subject to whole arm events (as both gains and losses) as well as regional deletions.

Alleles↗
PubMed1995

Loss of heterozygosity on the X chromosome in human breast cancer.

The analysis of loss of heterozygosity (LOH) in tumours can be a powerful tool for mapping the sites of tumour suppressor genes in the human genome. A panel of breast cancer patients was assembled as pairs of tumour and lymphocyte DNA samples and LOH studies carried out by Southern hybridisation with polymorphic loci mapping to the X chromosome with appropriate controls. Deletion mapping revealed a high frequency of small regionalised deletions, defining at least three independent regions, one of which is particularly well mapped to a 500 kb stretch of DNA in the distal portion of the pseudoautosomal region of Xp. A second region has been identified within the pseudoautosomal region close to the pseudoautosomal boundary, and there is a third discrete site of loss on distal Xq. Perturbations of sequences at these regions represent independent events in a number of patients. This study represents the first detailed analysis of LOH on the X chromosome in human breast tumours, the results of which indicate that at least three regions of this chromosome are involved in the disease.

Alleles↗
PubMed1995

Synergistic effects of IL-6 and IFN-gamma on carcinoembryonic antigen (CEA) and HLA expression by human colorectal carcinoma cells: role for endogenous IFN-beta.

When administered as single agents, both interferon gamma (IFN-gamma) and interleukin 6 (IL-6) significantly increase carcinoembryonic antigen (CEA) and HLA class I antigen expression on the surface of human colorectal tumour cells. Studies were carried out to determine whether by combining those cytokines a synergistic enhancement of CEA and HLA expression could result. The findings revealed that the administration of 20 units IFN-gamma along with 1.7 ng IL-6, concentrations of each cytokine that individually induced minimal antigenic changes, together synergistically increased CEA and HLA class I as well as induced qualitative changes in HLA expression on WiDr human colon carcinoma cells. The magnitude of the synergistic increases in CEA and HLA class I expression were reminiscent of the level of antigen augmentation observed when administering 20- to 100-fold higher amounts of each cytokine as a single agent. Also, the addition of IL-6 potentiated the IFN-gamma induction of HLA class II expression. The combined administration of IL-6 potentiated the IFN-gamma did not have any additive or synergistic effects on the growth suppression of those tumour cells. Interestingly, utilization of specific neutralizing antibodies for type I interferons abrogated the increases of CEA and HLA expression seen with IL-6 treatment alone or in combination with IFN-gamma. Moreover, reverse transcriptase/polymerase chain reaction analyses revealed a constitutive expression as well as a temporal increase of IFN-beta mRNA transcripts in colon tumour cells treated with IL-6. Therefore, the findings provide indirect evidence that IFN-beta production seems to play a critical role in the ability of IL-6 to upregulate antigen expression alone or in combination with IFN-gamma. These findings provide insight into cytokine combinations that synergistically upregulate tumour-associated and normal HLA antigen expression on the surface of human tumour cells. Those results provide the rationale for the combined use of such cytokines to heighten tumour cell recognition in monoclonal antibody- or cell-mediated-based immunotherapeutic approaches.

Antibodies, Monoclonal↗
PubMed1995

Genital-associated lymphoid tissue in female non-human primates.

We investigated genital-associated lymphoid tissue (GENALT) in non-human primates (macaques), by augmenting vaginal with oral immunization. The vaccine was a recombinant particulate SIV antigen (p27:Ty-VLP), linked to CT-B, and administered into the vagina by a paediatric naso-gastric tube and into the stomach by a gastric tube. Oro-vaginal or vagino-oral sequence of immunization elicited specific CD4+ T cell proliferative responses to p27 antigen in the genital lymph nodes and the spleen but not in unrelated lymph nodes. CD4+ T cells reconstituted with B cells and macrophages from the genital lymph nodes induced specific IgA and to a lesser extent IgG anti-p27 antibodies. However, the corresponding splenic cells induced greater IgG than IgA antibody synthesis. Intramuscular immunization primed splenic but not genital lymph node cells, and induced CD4+ T cell proliferative responses and predominantly B cell IgG antibody synthesis. Finding primed B and T cells in the genital lymph nodes after augmenting vaginal by oral immunization provides experimental evidence for GENALT in non-human primates. This primate model of vaginal immunization suggests 3 levels of specific immunity: (1) secretory IgA (and IgG) in the cervico-vaginal mucosal epithelium; (2) primed CD4+ T cells and B cells in the genital lymph nodes and the spleen; and (3) circulating CD4+ T cells, B cells and IgG and IgA antibodies specific to the immunizing antigen.

Administration, Intravaginal↗
PubMed1995

The [13C]acetate breath test accurately reflects gastric emptying of liquids in both liquid and semisolid test meals.

BACKGROUND/AIMS: The current standard for gastric emptying studies are radioactive isotope methods. [13C]breath tests have been developed as a nonradioactive alternative. The aim of this study was to validate a [13C]acetate breath test as a measure of gastric emptying of the liquid phase both in liquid and semisolid test meals by simultaneous radioscintigraphy. METHODS: Thirty-five patients with dyspeptic symptoms and 20 healthy volunteers were tested using a semisolid oatmeal or a liquid test meal. Both test meals were labeled by 150 mg sodium [13C]acetate and (in patients) by 45 MBq 99mTc-albumin colloid. Half-time of gastric emptying was calculated after curve fitting of the 13C exhalation to a modified power exponential function. 99mTc-albumin emptying was measured by conventional radioscintigraphy. RESULTS: The half-emptying times for the [13C]acetate breath test closely correlated to those measured by radioscintigraphy both for semisolids (r = 0.87) and liquids (r = 0.95). The time of maximum 13CO2 exhalation was itself a reliable parameter compared with the half-emptying times obtained by scintigraphy (r = 0.85 for semisolids; r = 0.94 for liquids). CONCLUSIONS: The [13C]acetate breath test is a reliable and noninvasive tool for the analysis of gastric emptying rates of liquid phases without radiation exposure.

Acetates↗
PubMed1995

Immunogenicity of the yeast recombinant p17/p24:Ty virus-like particles (p24-VLP) in healthy volunteers.

In this Phase I study, immunisation with the yeast-derived p24 virus-like particles Ty p24-VLP (3 x 100 or 3 x 500 micrograms subcutaneously) in 16 healthy male subjects elicited p24 antibody responses in 4 of 16 (25%) subjects. After a fourth, intramuscular, immunisation (500 micrograms), p24 antibody responses were detected in 11 of 15 (70%) subjects. In addition to p24 antibody responses, T cell proliferative responses were also observed, although no HLA restricted p24-specific cytotoxic T cell responses were detected. The results demonstrate that Ty p24-VLP is immunogenic and well-tolerated in healthy male subjects.

AIDS Vaccines↗
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↗