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Biomedical subjects

J Thompson

Publications and source records attributed to J Thompson.

At least 361 records · Page 20Linked to original sources

Inhalation challenge effects of perfume scent strips in patients with asthma.

BACKGROUND: Perfume- and cologne-scented advertisement strips are widely used. There are, however, very few data on the adverse effects of perfume inhalation in asthmatic subjects. OBJECTIVES: This study was undertaken to determine whether perfume inhalation from magazine scent strips could exacerbate asthma. METHODS: Twenty-nine asthmatic adults and 13 normal subjects were included in the study. Histories were obtained and physical examinations performed. Asthma severity was determined by clinical criteria of the National Heart, Lung, and Blood Institute (NHLBI). Skin prick tests with common inhalant allergens and with the perfume under investigation were also performed. Four bronchial inhalation challenges were performed on each subject using commercial perfume scented strips, filter paper impregnated with perfume identical to that of the commercial strips, 70% isopropyl alcohol, and normal saline, respectively. Symptoms and signs were recorded before and after challenges. Pulmonary function studies were performed before and at 10, 20, and 30 minutes after challenges. RESULTS: Inhalational challenges using perfume produced significant declines in FEV1 in asthmatic patients when compared with control subjects. No significant change in FEV1 was noted after saline (placebo) challenge in asthmatic patients. The percent decline in FEV1 was significantly greater after challenge in severely asthmatic patients as compared with those with mild asthma. Chest tightness and wheezing occurred in 20.7% of asthmatic patients after perfume challenges. Asthmatic exacerbations after perfume challenge occurred in 36%, 17%, and 8% of patients with severe, moderate, and mild asthma, respectively. Patients with atopic asthma had greater decreases in FEV1 after perfume challenge when compared with patients with nonallergic asthma. CONCLUSIONS: Perfume-scented strips in magazines can cause exacerbations of symptoms and airway obstruction in asthmatic patients. Severe and atopic asthma increases risk of adverse respiratory reactions to perfumes.

Administration, Inhalation↗

Innovation in general practice: is the gap between training and non-training practices getting wider?

BACKGROUND: Training practices are more developed than non-training practices in terms of a wide range of educational and clinical activities, facilities and staff. If training practices are also adopting new innovations at a faster rate than non-training practices the gap between them will increase. AIM: The aim of this study was to determine whether, between 1982 and 1990, training practices did develop at a faster rate than non-training practices. METHOD: In 1982 a questionnaire was sent to 153 practices in Gloucestershire, Avon and Somerset which all had one or more partners who were members of the Royal College of General Practitioners. A second questionnaire was sent to the same practices in 1990. Information was sought about practice features including organization, size, facilities, staff and clinical and educational activities. A total of 124 practices (62 training and non-training) completed questionnaires on both occasions. RESULTS: There were substantial changes in the cohort between the surveys in 1982 and 1990, with many practices gaining, for example, a practice manager, practice nurse and purpose built premises, and introducing audits, screening activities and specific clinics. For each feature of practice a logistic regression was undertaken with training used as an explanatory variable. Training practices were more likely to develop than non-training practices for a number of features including personnel, aspects of practice organization, educational activities, clinical activities and equipment. CONCLUSION: Training practices are not only more developed than non-training practices but are also more innovative. The gap between training and non-training practices did grow wider between 1982 and 1990. This may be because the members of training practices are inherently more innovative, face fewer obstacles to innovation or that the scheme for approval of practices for training has encouraged specific innovations. Any future accreditation scheme for general practices must be organized to encourage accelerated development in less developed practices rather than only stimulate innovation in already advanced practices.

Education, Medical, Continuing↗

Nasopharyngeal nonossifying variant of ossifying fibromyxoid tumor: CT and MR findings.

The CT and MR findings of a nasopharyngeal nonossifying variant of an ossifying fibromyxoid tumor are presented. The findings are radiographically indistinguishable from more common malignant neoplasms encountered in this region. The tumor was isointense with muscle on T1-weighted images. On proton density- and T2-weighted images, the mass was mostly isointense with gray matter but contained some areas of lower intensity that might reflect the fibrous tissue component. The tumor eroded through the floor of the middle cranial fossa.

Adult↗

IL-4 enhances IL-3 and IL-8 gene expression in a human leukemic mast cell line.

We examined the capacity of interleukin (IL)-4 to induce or enhance the expression of certain cytokines in resting and activated cells of the HMC-1 human leukemic mast cell line. The HMC-1 mast cells were cultured with or without recombinant human IL-4 and then activated with the calcium ionophore ionomycin. Stimulation of non-IL-4-treated cells with ionomycin (10 microM) for periods of 30 min to 8 hr induced expression of mRNA encoding IL-3, IL-4 and IL-8 but was without effect on levels of mRNA for tumour necrosis factor (TNF)-alpha or beta-actin. Culture of the cells with IL-4 (100 ng/ml) for 24 hr led to a small increase in resting levels of mRNA for IL-3 and IL-8 but not for IL-4, TNF-alpha or beta-actin. More notably, the IL-4 treatment produced a pronounced elevation of mRNA for IL-3 and IL-8 when the cells were subsequently activated with ionomycin. The IL-4 treatment produced a negligible effect on IL-4 mRNA, and no effect on TNF-alpha or beta-actin mRNA levels in ionomycin-activated cells. Quantitation of cDNA by competitive polymerase chain reaction (PCR) revealed that the IL-4 treatment produced a sixfold increase in ionomycin-induced levels of cellular IL-3 mRNA, a fourfold increase in induced IL-8 mRNA and less than a twofold increase in induced IL-4 mRNA. The IL-4 treatment led to a 15- to 20-fold increase in ionomycin-induced secretion of IL-3 product and a doubling of induced IL-8 product. These effects of IL-4 were not associated with increased mast cell numbers. We conclude that IL-4 alone is a weak activator of IL-3 and IL-8 gene expression in mast cells, but is able to enhance activation signals in stimulated mast cells leading to transcription and secretion of these two cytokines.

Base Sequence↗

Selective T cell depletion with CD8-conjugated magnetic beads in the prevention of graft-versus-host disease after allogeneic bone marrow transplantation.

The effects of a new immunomagnetic method of selectively depleting CD8+ lymphocytes from donor bone marrow were studied in 29 patients undergoing transplantation from HLA-identical sibling (n = 20) or alternative (n = 9) donors. The direct immunomagnetic depletion method consistently removed > 95% of CD8+ cells and the non-specific loss of other cell subsets was only about 15%. Recovery of CFU-GM and BFU-e was on average > 100%. The final graft contained 0.9 +/- 0.6 x 10(8)/kg nucleated cells and 1.4 +/- 2.7 x 10(5)/kg CD8+ cells. Patients also received cyclosporine starting day -1. Engraftment occurred in 28 patients (97%), including three patients who received a non-TBI conditioning regimen. One patient receiving an unrelated transplant failed to engraft. Median time to ANC > 500 x 10(6)/L was 17 (12-23) days. Four of 20 patients receiving grafts from HLA-identical siblings (20%) developed acute GVHD grade > or = II. However, five of eight patients with grafts from alternative donors (63%) had grade > or = II GVHD. Nearly all patients developed fever around day 7, accompanied by fluid overload, mild skin rash and shortness of breath. This syndrome necessitated treatment with steroids. Immunomagnetic CD8 depletion is a simple and reproducible method of selective T cell depletion. In combination with cyclosporine it appears to be effective in the prevention of severe acute GVHD in HLA-identical sibling transplants, but not in transplants from less perfectly matched donors.

Adult↗

Inhalation of nitric oxide. An innovative therapy for treatment of increased pulmonary vascular resistance.

Critical care of patients during pulmonary hypertensive crises is difficult and treatment is hazardous. Conventional therapy has relied on hyperventilation with oxygen and the use of nonselective intravenous vasodilators. The limitations of this approach have prompted clinical investigations of new therapeutic modalities based on recent advances in vascular biology. Inhaled nitric oxide can be used selectively to manipulate the pulmonary vasculature and treat a variety of pulmonary hypertensive disorders. Preliminary studies appear promising as results of properly conducted trials to evaluate efficacy and toxicity are awaited.

Administration, Inhalation↗

Identification of auto-transplanted parathyroid tissue by Tc-99m methoxy isobutyl isonitrile scintigraphy.

Parathyroid tissue is sometimes auto-transplanted into the forearm after 'total' parathyroidectomy in patients with renal failure. Recurrent hyperparathyroidism demands identification of the source of PTH secretion which cannot be assumed to be the forearm. To this end, Tc-99m methoxy isobutyl isonitrile (MIBI) scintigraphy was used to identify functioning auto-transplanted parathyroid tissue in seven patients undergoing renal replacement therapy (five with functioning renal transplants and two on haemodialysis). Serum PTH was estimated in venous blood taken proximal and distal to the forearm graft and from the contralateral arm, and subsequent Tc-99m MIBI scanning was carried out without knowledge of the PTH results. Five patients had a significant gradient in PTH levels between sites proximal and distal to the graft, and between the proximal site and the contralateral arm, suggesting functioning parathyroid tissue in the graft. Subsequent Tc-99m MIBI scintigraphy confirmed the activity of the auto-transplanted parathyroid tissue in these five patients. In the remaining two patients without a significant PTH gradient between the sampling sites, Tc-99m MIBI scintigraphy did not identify any functioning forearm parathyroid tissue. The scan results therefore correlated well with the gradients in PTH levels, suggesting that MIBI scintigraphy can be used to identify functioning auto-transplanted parathyroid tissue. The results also indicate that any patient who has undergone auto-transplantation of parathyroid tissue must have blood samples taken from veins proximal to the graft and either distal to it, or from the contralateral arm when parathyroid status is re-assessed, particularly when surgery is being considered for recurrent hyperparathyroidism.

Adult↗

CGM2, a member of the carcinoembryonic antigen gene family is down-regulated in colorectal carcinomas.

We have determined the precise chromosomal location, the exon structure, and the expression pattern of CGM2, a member of the carcinoembryonic antigen (CEA) gene family. CGM2 cDNA was amplified by reverse transcription-polymerase chain reaction (RT/PCR) from the colon adenocarcinoma cell line, LS174T. A defective exon is missing from this cDNA clone, leading to a novel domain organization for the human CEA family with two immunoglobulin-like domains. The derived C-terminal domain predicts that the CGM2 protein is membrane-bound through a glycosyl phosphatidylinositol anchor. RT/PCR analyses identified CGM2 transcripts in mucinous ovarian and colonic adenocarcinomas as well as in adjacent colonic tissue, but not in other tumors including leukocytes from six chronic myeloid leukemia patients. Thus, unlike several other family members, CGM2 is not expressed in granulocytes but reveals a more CEA-like expression pattern. Northern blot analyses identified a 2.5-kilobase CGM2 mRNA that is strongly down-regulated in colonic adenocarcinomas compared with adjacent colonic mucosa, suggesting a possible tumor suppressor function. In addition, a 3.2-kilobase transcript was observed in a number of colon tumors that is not detectable in normal colonic tissue. This mRNA species could represent a tumor-specific CGM2 splice variant.

Adenocarcinoma↗

Biodegradable estradiol microspheres do not affect uterine involution or characteristics of postpartum estrus in mares.

Quarterhorse mares were used to investigate effects of estradiol-17beta on uterine involution, duration of estrus, interval to ovulation, and fertility achieved by breeding on the first postpartum estrus. On the day of foaling, mares were injected with biodegradable poly (DL-lactide) microspheres containing either 100 mg estradiol-17beta (25 mares) or no drug (27 mares). The treatment period was considered to last for 12 to 15 d. Estrus was determined by teasing mares (n=16) with a stallion. Ovulation was detected by transrectal ultrasonographic examination of ovaries (n=48). On Days 6, 11 and 16 post partum, transrectal ultrasonography was used to measure cross-sectional diameters of the uterine body, uterine horns, and fluid within the uterine lumen (n=28). Uteri were swabbed for bacteriologic culture, and uterine biopsies were obtained from the previously gravid uterine horn on Days 11 and 16 post partum, for assessment of endometritis and morphometric analysis of endometrial histioarchitecture (n=19). Twenty-two mares were bred on foal-heat, and pregnancy was determined by transrectal ultrasonography on 14 to 16 and 30 to 35 d after breeding. With only one exception (diameter of previously gravid uterine horn on Day 11), mean values for all measures of uterine involution did not differ between treatment groups (P > 0.05). No differences were detected between treatment group means for length of estrus or interval to ovulation (P > 0.05). No differences were detected between treatment group liklihoods for recovery of potential bacterial pathogens, presence of endometritis, or presence of intrauterine fluid at 11 or 16 d post partum (P > 0.05). Pregnancy rate of mares treated with estradiol (5 11 ; 45%) was not different from that of control mares (9 11 ; 82%; P > 0.05). Estradiol treatment did not hasten uterine involution, increase duration of estrus, delay ovulation, or increase fertility in these postpartum mares.

Journal Article↗

Mice transgenic for the human carcinoembryonic antigen gene maintain its spatiotemporal expression pattern.

The tumor marker carcinoembryonic antigen (CEA) is predominantly expressed in epithelial cells along the gastrointestinal tract and in a variety of adenocarcinomas. As a basis for investigating its in vivo regulation and for establishing an animal model for tumor immunotherapy, transgenic mice were generated with a 33-kilobase cosmid clone insert containing the complete human CEA gene and flanking sequences. CEA was found in the tongue, esophagus, stomach, small intestine, cecum, colon, and trachea and at low levels in the lung, testis, and uterus of adult mice of independent transgenic strains. CEA was first detected at day 10.5 of embryonic development (embryonic day 10.5) in primary trophoblast giant cells and was found in the developing gut, urethra, trachea, lung, and nucleus pulposus of the vertebral column from embryonic day 14.5 onwards. From embryonic day 16.5 CEA was also visible in the nasal mucosa and tongue. Because this spatiotemporal expression pattern correlates well with that known for humans, it follows that the transferred genomic region contains all of the regulatory elements required for the correct expression of CEA. Furthermore, although mice apparently lack an endogenous CEA gene, the entire repertoire of transcription factors necessary for correct expression of the CEA transgene is conserved between mice and humans. After tumor induction, these immunocompetent mice will serve as a model for optimizing various forms of immunotherapy, using CEA as a target antigen.

Animals↗

The in-training examination in internal medicine.

OBJECTIVE: The In-Training Examination in Internal Medicine (ITE-IM) has been offered to internal medicine trainees annually since 1988 as an instrument for self-assessment. This report outlines the manner in which the test is prepared, reviews the results of annual examinations, and analyzes trends during the past 6 years. DESIGN: Results of each examination were reviewed with regard to the demographic characteristics of persons taking the test, their previous medical training, and their present program affiliations. RESULTS: Then number of residents participating in the ITE-IM has increased steadily over the past 6 years. In 1993, more than 12,000 residents from more than 90% of internal medicine training programs in the United States participated in the examination; the percentage of international medical school graduates taking the examination increased from 27% in 1988 to 47% in 1993. Statistical analyses of each examination have shown it to be reliable, internally consistent, and discriminating. Over the past 6 years, graduates of U.S. medical schools have scored consistently higher than those of international medical schools and schools of osteopathic medicine on all annual examinations. However, in 1993, for residents at all levels of training, the differences in scores between graduates of U.S. medical schools and graduates of international medical schools narrowed substantially. From 1988 to 1993, there has been a trend toward lower scores by every cohort on each subsequent examination. The decreases in scores are most pronounced for graduates of U.S. medical school and those of schools of osteopathic medicine. The lower scores may be caused by either an increased level of difficulty in the examination or decreased knowledge among examinees. CONCLUSIONS: The ITE-IM is a useful instrument to assess the knowledge base of residents and program directors with a reliable evaluation of themselves and their programs in comparison to their national peer groups. It also provides objective data to monitor trends over time in residents' scores and relates them to the changing demographic characteristics of trainees and to innovations in the clinical curricula of internal medicine training programs.

Clinical Competence↗

Transcriptional activation of minimal HIV-1 promoter by ORF-1 protein expressed from the SalI-L fragment of human herpesvirus 6.

The SalI-L fragment of human herpesvirus 6 (HHV-6) strain U1102 transformed rodent cells and transactivated the HIV-1 LTR 10- to 15-fold in both monkey fibroblasts and human T-lymphocytes. In this report, the SalI-L transactivator of the HIV-1 LTR was localized to ORF-1 which codes for a protein of 357 amino acids. To determine if ORF-1 required functional Sp1 binding sites or the TATA box element of HIV-1 LTR for transactivation, 5'-deletion mutants of the HIV-1 LTR were employed. Plasmids pBS/SalI-L, pBS/SalI-L-SH, and pC6/ORF-1(S), a mammalian expression vector containing ORF-1, all transactivated a deletion mutant of HIV-1 LTR lacking functional Sp1 binding sites (CD-54). These studies demonstrate that transactivation occurred in the absence of Sp1 binding sites and required only a minimal HIV-1 promoter which contains the TATA box element. The specificity of the SalI-L transactivator for HIV-1 LTR was demonstrated by its inability to transactivate the human papillomavirus type 16 or 18 early promoters. The ORF-1 gene was cloned into and expressed from the pET17b bacterial expression vector. Purified ORF-1 protein was obtained by ammonium sulfate precipitation, Mono-S chromatography, and anti-T7. Tag immunoaffinity chromatography. Transactivation of the HIV-1 LTR by ORF-1 protein was demonstrated by electroporation studies in vivo and by transcription studies in vitro. To substantiate the putative biological role of ORF-1, pBS/SalI-L, pBS/SalI-L-SH, and pC6/ORF-1 all reactivated tat-defective HIV-1 provirus from latently infected cells expressing CD4. Thus, the data presented suggest that HHV-6 infection could have a cofactor role in the progression of AIDS.

Amino Acid Sequence↗

Horizontal root fracture--an unusual complication.

Cystic change at the site of a root fracture is an unusual sequelae. A case report of such an occurrence in a horizontal root fracture involving the apical third of a permanent central incisor in a 22-year-old man is presented and management of these injuries is discussed in brief.

Adult↗

Laboratory study of HIV-1 and HTLV-I/II coinfection.

A Retroviral Coinfection Clinic was established in 1991 at Charity Hospital Medical Center of Louisiana to study patients dually infected with human immunodeficiency virus (HIV) and human T lymphotropic virus (HTLV-I, HTLV-II). Eight patients were evaluated clinically, and by immunological and virological studies. Multiple neuromuscular diseases were observed, including tropical spastic paraparesis, polymyositis, and polyneuropathies. Only one patient developed AIDS. HIV-1 infected patients with HTLV-I, but not HTLV-II, coinfection have maintained stable CD4 counts, despite the fact that quantitative HIV DNA PCR suggests a relatively high copy number. HTLV-I/II antigens were detected in lymphocyte cultures from four patients, and lymphoblastoid cell lines have been established from two. These results support the contention that upregulated HTLV-I/II virus expression and disease manifestations occur during coinfection with HIV, sometimes in association with normal CD4 counts.

Adult↗

A 79 amino acid oncogene is responsible for human cytomegalovirus mtrII induced malignant transformation.

Human cytomegalovirus (HCMV) morphological transforming region (mtr)II is the only HCMV mtr that was retained and expressed in transformed mouse or rat cells. The minimal transforming region has previously been shown to be within a 980-bp BanII/XhoI subfragment which encodes three open reading frames (ORF) of 34, 79, and 83 amino acids. This report provides definitive evidence that the 79-aa ORF is responsible for mtrII mediated tumorigenic transformation. The 79-aa ORF, subcloned into a mammalian expression vector, pCHC79orf, induced morphologic transformation of NIH 3T3 cells. These transformed cells expressed 79-aa ORF specific transcripts and were tumorigenic when injected into nude mice. A construct containing a triple termination linker inserted after codon 24 failed to transform NIH 3T3 cells to tumorigenicity even though 79-aa ORF specific transcripts were expressed. Furthermore, when the triple termination linker was inserted after codon 49, tumorigenic transformation still occurred. These results demonstrate that the 79-aa ORF is the oncogene within HCMV mtrII and that the first 49-aa are sufficient.

3T3 Cells↗