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Biomedical subjects

S Adams

Publications and source records attributed to S Adams.

At least 55 records · Page 3Linked to original sources
PubMed1997

Short segment Barrett's oesophagus: prevalence, diagnosis and associations.

BACKGROUND: Prevalence of short segment Barrett's (SSB) oesophagus, defined as the absence of macroscopic Barrett's but histologically identifiable intestinal metaplasia, has been reported to be 18% based on haematoxylin and eosin (H&E) staining. AIMS: To define the prevalence of SSB oesophagus using H&E and alcian blue staining and to determine whether SSB oesophagus is associated with inflammation at the gastro-oesophageal junction (GOJ). SUBJECTS: Consecutive patients (n = 158) presenting for endoscopy completed a structured interview. METHODS: Two biopsy specimens taken from the GOJ were stained with H&E, alcian blue and Giemsa. A third specimen was obtained from the distal oesophagus. Intestinal metaplasia was diagnosed if goblet cells were definitely identified by two independent observers. RESULTS: SSB oesophagus was present in 46 (prevalence 36%, 95% confidence interval (CI) 28.5-43.5) using alcian blue staining. If H&E had been the sole staining method used, 50% cases of intestinal metaplasia would have been overlooked. There were no cases of intestinal metaplasia identified by H&E but missed by alcian blue staining. Logistic regression analysis identified age (odds ratio (OR) per decade 1.03, 95% CI 1.01-1.06), histological oesophagitis (OR 3.2, 95% CI 1.4-7.2) and inflammation at the gastrooesophageal junction (OR 5.9, 95% CI 2.2-15.6) as independent risk factors for SSB oesophagus. CONCLUSION: Unrecognised SSB oesophagus is highly prevalent in patients presenting for diagnostic upper endoscopy if alcian blue staining is applied.

Adult↗
PubMed1997

Amplification of the t(2; 13) and t(1; 13) translocations of alveolar rhabdomyosarcoma in small formalin-fixed biopsies using a modified reverse transcriptase polymerase chain reaction.

Detection of characteristic chromosomal translocations has aided diagnosis of the small round cell tumors of childhood and may help to stratify patients into clinical groups. The detection of the abnormalities by classical cytogenetic techniques has been supplemented by fluorescent in situ hybridization and reverse transcriptase polymerase chain reaction (RT-PCR). These techniques allow diagnoses to be made using only very small amounts of tumor tissue. We here describe a technique for the rapid and specific detection by modified reverse transcriptase polymerase chain reaction of characteristic chromosomal translocations of alveolar rhabdomyosarcoma with small amounts of formalin-fixed tissue as the starting material. Of 27 samples studied, 4 cases are described in which the detection of translocations by this method cast doubt on the original histopathological diagnosis. These cases demonstrate the critical diagnostic importance of the detection of these translocations in rhabdomyosarcoma.

Adolescent↗
PubMed1997

[Pre- and intraoperative localization of neuroendocrine tumors].

Previous studies of the intraoperative use of a hand-held gamma probe to localize metastases and primary tumors of colorectal cancer have shown improved assessment of tumor spread and changes in surgical management based on added information gained by radioimmunoguided surgery. Following the injection of 180 MBq [111In-DTPA-D-Phe1]-pentetreotide and/or 500 MBq 99mTc-dimercaptosuccinic acid (both for dual-radionuclide scintigraphy) preoperative somatostatin receptor imaging [11 patients with GEP tumors] and dual-radionuclide scintigraphy. (8 patients with relapsing medullary thyroid carcinomas) was performed. One patient with a metastasizing pheochromocytoma underwent 123]-MIBg scintigraphy. Results were combined with the information obtained from conventional imaging modalities. Intraoperative radiodetection was performed 24 hours after administration of [111In-DTPA-D-Phe1]-pentetreotide or 4 hours following the injection of 99mTc(V)DMSA using a hand-held gamma probe (Tec Probe 2000. Stratec, FRG). Intraoperative gamma counting localized 39 somatostatin receptor positive lesions of GEP tumors whereas preoperative receptor imaging visualized 81%, surgical palpation 41% and radiological imaging modalities localized only 31%. In 8 patients with recurrent medullary thyroid carcinoma the surgeon was successful in localizing and removing 18 tumor lesions by the help of the gamma probe. Dual-radionuclide scintigraphy revealed 77% (Octreoscan 5/18; 99mTc-V-DMSA 9/18), surgical palpation 55% and conventional imaging methods (CT, sonography) only 38% of all lesions detected intraoperatively by the hand-held gamma probe. In summary, this preliminary data show that intraoperative hand-held gamma probe detection of microscopic and occult endocrine tumors is feasible and more sensitive than external scintigraphy and conventional imaging.

Adrenal Gland Neoplasms↗
PubMed1997

Biological activity and therapeutic potential of homologs of an Ii peptide which regulates antigenic peptide binding to cell surface MHC class II molecules.

An invariant chain peptide (murine Ii76-92; Ii-Key) is known to produce a 10 to 50 times baseline enhancement of the presentation of specific antigenic peptides to murine T cell hybridomas by cell surface MHC class II molecules. In order to define structure-activity relationships in Ii-key, homologs were synthesized with the following systematic variations: 1) N- and C-terminal truncations, 2) N-terminal acetylation and C-terminal amidation, 3) substitutions with 13 natural amino acids in each position of the shortest, fully active peptide, and then with an additional 12 nonnatural amino acids at certain 'pharmacophore' positions, 4) substitutions with D-amino acids and N-methyl-leucine, and 5) cyclical forms. More than 160 homologs were tested for effects on antigen presentation by the murine MHC class II alleles: A(d), Ak, E(d), or Ek. For some compounds, allele specificity between E(d) and Ek exceeded 1:20. D-Amino acid and/or N-methyl-leucine substitutions were accepted at some residue positions, leading to peptides with relatively long half-lives in mouse serum and low toxicities in mice. An Ii-Key homolog inhibited in vitro presentation of an internally processed hen egg lysozyme determinant to a specific T hybridoma. The best compounds can be tested in vivo for therapeutic applications: 1) immunosuppression upon release of antigenic peptide, and 2) vaccination or immunomodulation upon co-administration of a second antigenic peptide.

Amino Acid Sequence↗
PubMed1996

Serum relaxin and the major endometrial secretory proteins in in-vitro fertilization and down-regulated hormone-supported and natural cycle frozen embryo transfer.

Relaxin has been postulated to be a modulator of the expression of the endometrial secretory proteins, insulin-like growth factor binding protein (IGFBP-1) and placental protein 14 (PP14). This study evaluated the expression of relaxin in relation to concentrations of these secretory proteins along with oestradiol, progesterone and human chorionic gonadotrophin in groups of pregnant and non-pregnant patients who underwent differing assisted conception treatments. Serum samples were taken from 88 patients at 8 and 12 days after embryo transfer. At 12 days after embryo transfer, relaxin concentrations in the pregnant patients who had undergone in-vitro fertilization (IVF) or natural cycle frozen embryo transfer were significantly higher than those who did not conceive in these groups (mean concentrations 8334 versus 28 and 2608 versus 62 pg/ml respectively, P<0.001). However concentrations in the pregnant patients who had hormone support and transfer of frozen embryos were not significantly different from the patients who did not conceive after the same treatment. Although relaxin expression was associated with corpus luteum activity, it was not related to the number of corpora lutea in IVF patients. A wide range of relaxin concentrations was seen to be compatible with a healthy pregnancy. These serum relaxin concentrations were not found to be directly related to the serum concentrations of IGFBP-1, PP14 or the other factors assessed in this study.

Chorionic Gonadotropin↗
PubMed1996

Caring for the pregnant woman with sickle cell crisis.

Pregnancy poses particular risks for women with sickle cell disease and their unborn babies. There is an increased risk of spontaneous abortion and preterm labour. Painful sickle cell crises tend to occur more frequently during pregnancy. A district-wide protocol for dealing with crises would help ensure the woman receives prompt, effective, knowledgeable care from GPs, midwives and A&E staff. Careful assessment is essential and hospital admission is usually required. Adequate relief of pain, and sometimes blood transfusions, are the cornerstones of treatment. Health education plays a part in prevention of crises. Care could be improved by more specialist centres and specialist nurses or midwives.

Acute Disease↗
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↗