Coeliac disease presenting with colonic lymphoma.
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Celiac Disease↗
Biomedical subjects
A Armstrong
Publications and source records attributed to A Armstrong.
Developing effective cancer vaccines: design and monitoring are critical.
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Antibodies, Anti-Idiotypic↗
A randomized controlled trial assessing the effect of heated carbon dioxide for insufflation on pain and recovery after laparoscopic fundoplication.
BACKGROUND: Insufflation with heated gas for laparoscopy may reduce postoperative pain. This study assessed the effect of heated gas on outcome after fundoplication. METHODS: A blinded, randomized trial compared the effect of heated or standard carbon dioxide (CO2) on core temperature, postoperative pain, analgesic requirement, and postoperative recovery. Pain scores were assessed with a 100 mm visual analog scale (VAS). Recovery was assessed with a patient diary and clinical follow-up assessment at 8 days and 1 month postoperatively. RESULTS: For this study, 40 patients were randomized to heated CO2 (n = 19) and standard CO2 (control) (n = 21) groups. The heated CO2 group increased core body temperature from 35.9 degrees to 36.1 degrees C, (p = 0.008), whereas the control group maintained core temperature at 35.8 degrees C. The control group had lower analgesic requirements and pain scores, significant at 12 h (VAS: 20 vs 36 mm; p = 0.04). There was no difference between the groups in terms of late recovery. The heated CO2 group showed a significant correlation between operative duration and requirement for postoperative morphine (p = 0.01). CONCLUSIONS: Heated gas provides no benefit for patients and may be associated with increased early pain. The elevation of core body temperature observed with heated CO2 is of little clinical significance.
Adult↗
Cloning of human thymic stromal lymphopoietin (TSLP) and signaling mechanisms leading to proliferation.
Thymic stromal lymphopoietin (TSLP) is a novel cytokine that was found to promote the development of murine B cells in vitro. Here we describe the cloning and characterization of the human homologue of murine TSLP. This protein, which is expressed in a number of tissues including heart, liver and prostate, prevented apoptosis and stimulated growth of the human acute myeloid leukemia (AML)-derived cell line MUTZ-3. Anti-interleukin (IL)-7 receptor antibodies (Abs) neutralized this effect indicating that TSLP binds to at least part of the IL-7 receptor complex. TSLP induced phosphorylation of signal transducer and activator of transcription (STAT)-5. In contrast to IL-7, TSLP-triggered STAT-5 phosphorylation was not preceded by activation of janus kinase (JAK) 3. These findings would be in accordance with the notion, raised previously for the mouse system, that TSLP leads to STAT-5 phosphorylation by activating other kinases than the JAKs. Some other signaling pathways stimulated by many cytokines are not involved in TSLP activity; thus, TSLP did not stimulate activation of ERK1,2 and p70S6K. Furthermore, neutralizing Abs raised against cytokines known to stimulate the growth of MUTZ-3 cells did not inhibit the proliferative effects of TSLP, suggesting that TSLP-induced growth was a direct effect. In summary, we describe the cloning of human TSLP and its proliferative effects on a myeloid cell line. TSLP-induced proliferation is preceded by phosphorylation of STAT-5, but not of JAK 3.
Amino Acid Sequence↗
B-lymphotropic viruses in a novel tropical splenic lymphoma.
Peripheral blood from patients with a novel tropical splenic lymphoma, characterized by splenomegaly and circulating naïve CD5-negative villous B lymphocytes, has been screened for evidence of an association with the B-lymphotropic viruses, Epstein--Barr virus (EBV), hepatitis C virus (HCV) and human herpesvirus 8 (HHV8). No increased prevalence of EBV, HCV and HHV8 was demonstrated using serological and molecular techniques, compared with a geographical, age-matched control group. However, lymphoma patients had markedly raised EBV antibody levels without a concomitant increase in the rate of detection of viral genomes in the peripheral blood. This phenomenon also occurred in patients with hyper-reactive malarial splenomegaly, a condition that occurs in the same geographical area and that is clinically indistinguishable from tropical splenic lymphoma, adding further weight to the suggestion that there may be an aetiological association between these two disorders.
Adolescent↗
Total synthesis of (+)-zaragozic acid C.
A total synthesis of (+)-zaragozic acid C is described. Key features of the synthesis are the use of a double Sharpless asymmetric dihydroxylation reaction of diene 6 to control stereochemistry at four contiguous stereocenters from C3 to C6; the introduction of the C1-side chain by reaction between the anion derived from the dithiane monosulfoxide 27 and the core aldehyde 12; a high yielding, acid-mediated simultaneous acetonide deprotection-dithiane removal-ketalization procedure leading exclusively to the 2, 8-dioxabicyclo[3.2.1]octane core 34; and a novel triple oxidation procedure allowing installation of the tricarboxylic acid.
Anticholesteremic Agents↗
Identification of CD7 as a cognate of the human K12 (SECTM1) protein.
CD7 is a 40-kDa protein found primarily on T, NK, and pre-B cells; the function of the CD7 protein in the immune system is largely unknown. The K12 (SECTM1) protein was originally identified by its location just upstream of the CD7 locus. The K12 gene encodes a transmembrane protein of unknown function. In order to clone a K12-binding protein, we generated a soluble version of the human K12 protein by fusing its extracellular domain to the Fc portion of human IgG(1). Flow cytometry experiments showed that the K12-Fc fusion protein bound at high levels to both human T and NK cells. Precipitation experiments using K12-Fc on (35)S-radiolabeled NK cells lysates indicated that the K12 cognate was an approximately 40-kDa protein. A human peripheral blood T cell cDNA expression library was screened with the K12-Fc protein, and two independent, positive cDNA clones were identified and sequenced. Both cDNAs encoded the same protein, which was CD7. Thus, K12 and CD7 are cognate proteins that are located next to each other on human chromosome 17q25. Additionally, we have cloned the gene encoding the mouse homologue of K12, shown that it maps near the mouse CD7 gene on chromosome 11, and established that the mouse K12 protein binds to mouse, but not human, CD7. Mouse K12-Fc inhibited in a dose-dependent manner concanavalin A-induced proliferation, but not anti-TcRalpha/beta induced proliferation, of mouse lymph node T cells. Human K12-Fc stimulated the up-regulation of CD25, CD54, and CD69 on human NK cells in vitro.
Amino Acid Sequence↗
Modulation of endometrial steroid receptors and growth regulatory genes by tamoxifen.
OBJECTIVE: We investigated tamoxifen's effects on the expression of growth regulatory genes in the endometrium to identify the mechanism by which tamoxifen induces proliferation. METHODS: Using immunohistochemical techniques, we analyzed 39 endometrial specimens for expression of Ki-67, lactoferrin, transforming growth factor-alpha, tumor necrosis factor receptor-II, adrenomedullin, estrogen receptors, and progesterone receptors. Twenty specimens were obtained from postmenopausal breast cancer patients treated with tamoxifen (20 mg/day) for at least 6 months to include two endometrial adenocarcinoma specimens. Five secretory phase, three proliferative phase, and seven atrophic endometrial specimens were used as controls. In addition, four endometrial adenocarcinoma specimens were reviewed from patients not treated with tamoxifen. Intensity of immunostaining was quantified using digitized imaging techniques. RESULTS: Overexpression of both estrogen receptors and progesterone receptors, and an elevated proliferative index were the most consistent effects observed in benign endometrial specimens from tamoxifen-treated patients compared with atrophic controls (P <. 003). This staining pattern was also evident in adenocarcinomas from patients who received tamoxifen. Benign endometrium from tamoxifen-treated patients also expressed transforming growth factor-alpha, tumor necrosis factor receptor-II, lactoferrin, and adrenomedullin at levels comparable with those found in proliferative endometrial specimens. CONCLUSION: These data provide further documentation that the uterotropic effects of tamoxifen may be due, at least in part, to the induction of estrogen receptors and progesterone receptors, as well as other genes associated with the proliferative phase. Furthermore, analysis of estrogen receptors, progesterone receptors, and Ki-67 may be useful in identifying postmenopausal individuals on tamoxifen, who are at increased risk for developing endometrial cancer.
Adrenomedullin↗
RANK is essential for osteoclast and lymph node development.
The physiological role of the TNF receptor (TNFR) family member, RANK, was investigated by generating RANK-deficient mice. RANK(-/-) mice were characterized by profound osteopetrosis resulting from an apparent block in osteoclast differentiation. RANK expression was not required for the commitment, differentiation, and functional maturation of macrophages and dendritic cells from their myeloid precursors but provided a necessary and specific signal for the differentiation of myeloid-derived osteoclasts. RANK(-/-) mice also exhibited a marked deficiency of B cells in the spleen. RANK(-/-) mice retained mucosal-associated lymphoid tissues including Peyer's patches but completely lacked all other peripheral lymph nodes, highlighting an additional major role for RANK in lymph node formation. These experiments reveal that RANK provides critical signals necessary for lymph node organogenesis and osteoclast differentiation.
Animals↗
Demonstration by ultraviolet resonance Raman spectroscopy of differences in DNA organization and interactions in filamentous viruses Pf1 and fd.
Pf1, a class II filamentous virus, has been investigated by ultraviolet resonance Raman (UVRR) spectroscopy with excitation wavelengths of 257, 244, 238, and 229 nm. The 257-nm UVRR spectrum is rich in Raman bands of the packaged single-stranded DNA (ssDNA) genome, despite the low DNA mass (6%) of the virion. Conversely, the 229-nm UVRR spectrum is dominated by tyrosines (Tyr 25 and Tyr 40) of the 46-residue alpha-helical coat subunit. UVRR spectra excited at 244 and 238 nm exhibit Raman bands diagnostic of both viral DNA and coat protein tyrosines. Raman markers of packaged Pf1 DNA contrast sharply with those of the DNA packaged in the class I filamentous virus fd [Wen, Z. Q., Overman, S. A., and Thomas, G. J., Jr. (1997) Biochemistry 36, 7810-7820]. Interestingly, deoxynucleotides of Pf1 DNA exhibit sugars in the C2'-endo/anti conformation and bases that are largely unstacked, compared with C3'-endo/anti conformers and very strong base stacking in fd DNA; hydrogen-bonding interactions of thymine carbonyls are also different in Pf1 and fd. On the other hand, coat protein tyrosines of Pf1 exhibit Raman markers of ring environment identical to those of fd, including an anomalous singlet at 853 cm-1 in lieu of the canonical Fermi doublet (850/830 cm-1) found in globular proteins. The results indicate markedly different modes of organization of ssDNA in Pf1 and fd virions, despite similar environments for coat protein tyrosines, and suggest strong hydrogen-bonding interactions between DNA bases and coat subunits of Pf1 but not between those of fd. We propose that structural relationships between the protein coat and encapsidated ssDNA genome are also fundamentally different in the two assemblies.
Capsid↗
Psychological characteristics of people with perceived food intolerance in a community sample.
In most adults who believe themselves to be food intolerant there is no objective supporting evidence. It has therefore been proposed that the misperception of intolerance to food is linked to psychiatric illness or personality disorder. This hypothesis was tested in a community-derived sample of individuals who attributed an adverse symptom to a type of food. A random mailing recruited 955 participants aged > or =18 years, of whom 232 perceived themselves to be food intolerant (PFI). All recruits were sent two questionnaires, the General Health Questionnaire-28 (GHQ-28) and the shortened version of the Eysenck Personality Questionnaire (EPQ-R). A total of 535 GHQ-28 and 518 EPQ-R forms were returned that were correctly completed, an overall response rate of 55%. For the subscales of the EPQ-R, neuroticism was greater in those with a PFI than those without. Women with a PFI were more extroverted than control women. For the GHQ-28 subscales, women with a PFI had significantly higher scores than control women on somatic symptoms, anxiety, insomnia, and severe depression. There was a greater percentage of psychiatric caseness among women with a PFI than among men with a PFI or control women. Nevertheless, this percentage was no greater than that reported among a reference sample derived from NHS and university staff. It is concluded that perceived food intolerance is associated with psychological distress in women with a PFI, and neurotic symptoms in both men and women with a PFI, but there is no greater prevalence of psychiatric disorder among women or men with a PFI than there is in some professional groups.
Adult↗
Retropharyngeal and mediastinal abscesses: postanesthetic complication of gynecologic surgery.
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Abscess↗
Enforced medication and virtue-ethics.
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Antipsychotic Agents↗
Seroreactivity to human papillomavirus types 16, 18, 31, and 45 virus-like particles in a case-control study of cervical squamous intraepithelial lesions.
Serum IgG antibodies to human papillomavirus (HPV) types 16, 18, 31, and 45 virus-like particles were measured in a nested case-control study of cervical squamous intraepithelial lesions. HPV-16 seroreactivity was strongly associated with HPV-16 DNA detection (odds ratio, 9.0; 95% confidence interval, 4.4-19.4), and similar type specificity was observed for HPV-31 and -45. In contrast, seroreactivity to any type was associated with elevated seroreactivity to all others. Among cases and controls, HPV-16 showed the highest seroprevalence, with 23.8% of 80 cases and 10.5% of 258 controls seroreactive to HPV-16 alone, and another 27.5% and 5.4%, respectively, seroreactive to HPV-16 plus other types. Overall, 24 (30.0%) cases and 17 (6.6%) controls were seroreactive to multiple types. These data suggest that seroreactivity to a given type reflects mainly type-specific HPV infection as measured by DNA detection and may also signal past exposure to other types that are now only serologically detected.
Antibodies, Viral↗
A randomized, double-blind crossover trial of sertraline in women with chronic pelvic pain.
The efficacy of antidepressants as analgesics for a range of chronic pain problems is well documented. However, a controlled trial of an antidepressant for women with chronic pelvic pain has not yet been published. We randomized 23 women from a general gynecology clinic to either double-blind sertraline or placebo. Measures of psychological function, pain, and functional disability were taken at baseline and 6 weeks. After a 2-week washout, the groups were crossed-over and the same measures were done over the next 6 weeks. There were no significant improvements in pain or functional disability noted on sertraline compared to placebo. Studies involving larger samples of patients are needed to confirm these findings.
1-Naphthylamine↗
The effects of tamoxifen on endometrial insulin-like growth factor-1 expression.
OBJECTIVE: To determine whether modulation of insulin-like growth factor-1 and insulin-like growth factor-binding protein-1 expression underlies the uterotropic effects associated with tamoxifen therapy in postmenopausal breast cancer patients. METHODS: Using immunohistochemical techniques, we analyzed 37 endometrial specimens from biopsies (n = 18) or hysterectomies (n = 19) for Ki-67, insulin-like growth factor-1, and insulin-like growth factor-binding protein-1 expression. Specifically, five secretory- and three proliferative-phase endometrial specimens were used as controls; 20 specimens (including two endometrial adenocarcinomas) were analyzed from postmenopausal breast cancer patients treated with tamoxifen (20 mg/day) for at least 6 months; and nine endometrial adenocarcinoma specimens from patients not treated with tamoxifen were studied. Intensity of immunostaining was quantified using digitized imaging techniques. RESULTS: Insulin-like growth factor-1 and insulin-like growth factor-1-binding protein-1 were found to be expressed in normal and neoplastic endometrium of all patients, regardless of tamoxifen treatment. However, insulin-like growth factor-1 expression varied cyclically in histologically normal endometrium, was reduced in undifferentiated endometrial tumors, and was upregulated in tamoxifen-treated specimens. Insulin-like growth factor-binding protein-1 immunostaining did not vary during the menstrual cycle, but it was reduced significantly in benign tamoxifen-exposed tissue and endometrial adenocarcinomas, regardless of degree of differentiation or tamoxifen exposure. No correlation was found between the expression of insulin-like growth factor-1 and insulin-like growth factor-binding protein-1 and the proliferative indices of the tissues examined. CONCLUSION: The expression of insulin-like growth factor-1 and insulin-like growth factor-binding protein-1 in the uterus supports an autocrine and/or paracrine role for these proteins in endometrial physiology. Although further studies are needed, our investigation suggests that altered expression of insulin-like growth factor-1 and insulin-like growth factor-binding protein-1 may contribute to the uterotropic effects of tamoxifen.
Adenocarcinoma↗
Predictors of performance on the National Board of Medical Examiners obstetrics and gynecology subject examination.
OBJECTIVE: To examine the correlation among the National Board of Medical Examiners subject examination, the US Medical Licensure Examination step 1 scores, and grade point average and to determine if poor performance could be predicted by the US Medical Licensure Examination step 1 score and grade point average. METHODS: The subject examination scores of 148 third-year medical students were compared with their US Medical Licensure Examination step 1 scores and grade point averages. Scores below the 20th percentile were defined as poor performance. RESULTS: There was a significant correlation between the US Medical Licensure Examination score and the subject examination score (r = .6, P < .001). The correlation with grade point average was also significant (r = .57, P < .001). CONCLUSION: The US Medical Licensure Examination step 1 performance, grade point average, and performance on the subject examination are all correlated. However, use of the US Medical Licensure Examination step 1 scores and grade point averages to identify all students at risk was associated with a high false-positive rate at our institution.
Certification↗
Age-related pregnancy rates in GIFT patients.
OBJECTIVE: Fecundity and fertility decline with increasing age beginning as early as age 30 and decrease more precipitously after age 40. The purpose of this study was to determine if pregnancy rates of patients attempting gamete intrafallopian transfer (GIFT) are lower for women between the ages of 35 and 40. METHODS: A retrospective chart review was performed to assess the age-specific pregnancy rates for patients in our GIFT program. We report the results of GIFT at Walter Reed Army Medical Center and the National Naval Medical Center during the period from July 1, 1994, to July 1, 1995. RESULTS: Fifty-six women aged 21 to 39 underwent one to three cycles of gamete intrafallopian transfer. The 72 tubal transfers performed resulted in 25 pregnancies (34.7% pregnancy rate per transfer). CONCLUSIONS: In this series, pregnancy rates did not differ significantly in women older than 35 years versus women younger than 35 years. The number of eggs collected decreased significantly with increasing age but was not significantly different between pregnant and nonpregnant patients. Previous reports demonstrate a clear decline in fertility and poor pregnancy rates with assisted reproductive technology in older women. We did not find age-related differences in pregnancy rates among women younger than 40 years undergoing GIFT during the period studied.
Adult↗