Biomedical subjects

W Stevens

Publications and source records attributed to W Stevens.

At least 55 records · Page 3Linked to original sources

PubMed1996

[New hypotheses in asthma: the mastocytes].

Increasing progress has been made in the understanding of the biology of mast cells. The precursors of mast cells leave the bone marrow in a non-differentiated form as CD34+ cells. The presence of mast cells growth and differentiation factors controls in tissues maturation of different mast cells phenotypes. The main factors are the mast cell growth factor SCF (stem cell factor), NGF (Nerve Growth Factor), and IL-3 (Interleukin-3). The potential role of each of these factors in the airways is discussed. An altered production of these growth factors in the airways of asthmatic patients might be the cause of the presence of an increased number of mast cells and of phenotypic modifications in the bronchi of these patients.

Asthma↗

PubMed1995

Sequence and functional characterization of the terminal exon of the human insulin receptor gene.

We present 5.1 kb of the 3' noncoding region sequence of the human insulin receptor gene and identification of four functional polyadenylation domains responsible for 3'-end processing of the 5.4, 6.9, 8.0 and 9.4 kb human insulin receptor mRNA, respectively. The insulin receptor gene contains five putative polyadenylation sites (P1-P5), located 5160, 6502, 7488, 8945 and 8957 base pairs (bp) downstream from the translational initiation site. All putative polyadenylation sites are flanked by upstream AU rich and downstream GU rich regions which regulate mRNA stability and mRNA cleavage, respectively. Also, two RNA stem-loop structures have been identified. To determine its role on gene expression, a reporter gene was constructed containing various lengths of the insulin receptor 3' UTR and transiently transfected into COS 7 cells. A 539 bp fragment (4897-5436 bp downstream from the IR translational initiation site) inhibited CAT expression by 5-6 fold. Further downstream addition of 1169 bp of the insulin receptor 3' untranslated region enhanced gene expression by 2-fold. These studies provide evidence that the insulin receptor 3' untranslated region can modulate gene expression.

Base Sequence↗

PubMed1995

The Utah Leukemia Case-Control Study: dosimetry methodology and results.

This paper discusses the dosimetry methodology used to estimate bone marrow dose and the results of dosimetry calculations for 6,507 subjects in an epidemiologic case-control study of leukemia among Utah residents. The estimated doses were used to determine if a higher incidence of leukemia among residents of Utah could have been attributed to exposure to radioactive fallout from above-ground nuclear weapons tests conducted at the Nevada Test Site. The objective of the dosimetry methodology was to estimate absorbed dose to active marrow specific to each case and each control subject. Data on the residence of each subject were available from records of the Church of Jesus Christ of Latter-day Saints. Deposition of fallout was determined from databases developed using historical measurements and exposure for each subject from each test was estimated using those data. Exposure was converted to dose by applying an age-dependent dose conversion factor and a factor for shielding. The median dose for all case and control subjects was 3.2 mGy. The maximum estimated mean dose for any case or control was 29 +/- 5.6 mGy (a resident of Washington County, UT). Uncertainties were estimated for each estimated dose. The results of the dosimetry calculations were applied in an epidemiological analysis.

Adolescent↗

PubMed1995

The Utah Thyroid Cohort Study: analysis of the dosimetry results.

Above ground testing of nuclear weapons at the Nevada Test Site (NTS) during the 1950s created radioactive fallout that was dispersed into the atmosphere and deposited over a large geographical area of the U.S. One area believed to have received a considerable amount of exposure to radioiodines (131I and 133I) in the fallout was southwest Utah and southeast Nevada. This paper describes the estimates of doses to the thyroid for a cohort of 3,545 subjects who were children during the atmospheric testing period. This group of children was examined for thyroid disease during 1965-1970 and again in 1985-1986. The cohort was made up of children who lived in three counties in 1965: Washington County, Utah; Lincoln County, Nevada; and Graham County, Arizona (originally thought to be an unexposed group). Pathway analysis was used in the dosimetry, considering exposures through the ingestion of milk and vegetables, inhalation of iodine during the passage of the fallout cloud, and external exposure. Specific data were obtained on diet (including sources and levels of milk and vegetables consumed, residence history, and lifestyle) by interviewing the parents or nearest living relative of subjects. The final dosimetry file for each member of the cohort contained specific doses to the thyroid glands and uncertainties (reported as geometric standard deviations, GSD) related to each dose estimate. The mean absorbed dose to the thyroid for subjects living in Washington County, Utah, was 170 mGy; for Lincoln County, Nevada, 50 mGy; and for those living in Graham County, Arizona, 13 mGy. The maximum dose to any subject was 4,610 mGy. There were 10 subjects who had doses greater than 1 Gy. The majority of uncertainty values calculated in this study were GSD values between 2.0 and 4.0. The results of the dosimetry were combined with the results of clinical examinations of the cohort to determine if a causal relationship exists between dose to thyroid from NTS generated radioactive iodines and the incidence of thyroid disease.

Adult↗

PubMed1994

Seasonal variation in peripheral blood leukocyte subsets and in serum interleukin-6, and soluble interleukin-2 and -6 receptor concentrations in normal volunteers.

This study has been carried out in order to investigate seasonal variation in peripheral blood immune cells, such as leukocytes, monocytes, neutrophils, lymphocytes, CD3+ T, CD4+ T, CD8+ T, CD25+ T, CD20+ B, and serum interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6R) and sIL-2R levels in normal volunteers. Toward this end, 26 normal volunteers (13 men, 13 women) had monthly blood samplings during one calendar year for peripheral blood count, flow cytometric enumeration of peripheral leukocyte subsets and immunoassays of IL-6, sIL-6R and sIL-2R. It was found that most of the immune variables change rhythmically during the seasons as a group phenomenon. Statistically significant yearly variations with seasonal rhythms, i.e. annual rhythms or harmonics, such as semiannual, tetramensual and trimensual rhythms, were found in the number of leukocytes, neutrophils, monocytes, lymphocytes, CD4+ T, CD8+ T, CD25+ T, CD20+ B cells, in the CD4+/CD8+ ratio, and serum IL-6 and sIL-6R levels. It is concluded that the immune system is characterized by a multifrequency time-structure with significant high-amplitude yearly variations in the number of some peripheral blood leukocyte subsets.

Antigens, CD↗

PubMed1994

Natural killer cell activity in major depression: relation to circulating natural killer cells, cellular indices of the immune response, and depressive phenomenology.

1. Recently, blunted natural killer cell activity (NKCA) has been found in major depression. The present study investigates the relationships between ex vivo blunted NKCA in major depression, number or percentage of NKC, in vivo indices of systemic immune activation and depressive phenomenology. 2. Toward this end, NKCA, absolute number of leukocytes and number or percentage of lymphocytes, monocytes, neutrophils, activated T lymphocytes (HLA-DR+, CD25+) and NKC (CD3-CD56+) were determined in 13 normal controls and 36 depressed inpatients. 3. NKCA was significantly and positively related to number and percentage of NKC in the peripheral blood. The major depression-related reduction in NKCA was not related to alterations in peripheral NKC. There were significant negative correlations between NKCA and number or percentage of leukocytes, monocytes, neutrophils and HLA-DR+ T cells. Up to 50% of the variance in NKCA could be explained by the regression on the number of monocytes, percentage of HLA-DR+ T and NKC cells, and diagnostic classification. Up to 43% of the variance in NKCA was explained by depressed mood, somatic anxiety and less diurnal variation. 4. The results show that blunted NKCA in major depression is not related to alterations in peripheral NKC, but reflects in part the systemic immune activation in that illness.

Adult↗

PubMed1994

Multiple reciprocal relationships between in vivo cellular immunity and hypothalamic-pituitary-adrenal axis in depression.

Major depression is reportedly characterized by increased activity of the hypothalamic-pituitary-adrenal (HPA) axis and by in vivo immune activation. The present study was carried out in order to investigate the relationships between HPA-axis activity and in vivo immune function in depression. Towards this end the following parameters were measured: 24 h urinary cortisol (UC) excretion; basal and post-dexamethasone (DST) plasma cortisol, beta-endorphin/beta-lipotropin (beta END/beta LPH) and dexamethasone concentrations; and leucocyte subsets (i.e. lymphocytes, neutrophils, monocytes, CD4+, CD4+CD45RA+, CD4+CD45RO+, CD8+, CD8+CD57+, CD8+CD57-, HLA-DR+, CD25+ T cells, HLA-DR+, CD19+, CD20+, and CD21+ B cells) both pre- and post-DST. Dexamethasone administration (1 mg orally) induced leucocytosis, lymphocytopaenia, monocytopaenia and neutrophilia. HPA-axis non-suppressors exhibited a relative resistance to the enhancing (e.g. neutrophils) or depressant (e.g. lymphocytes, CD4+ T cells) effects of dexamethasone. There were significant correlations between UC excretion and the number of percentage of lymphocytes, monocytes, CD4+CD45RA+ and CD8+CD57- T cells (negatively) and neutrophils (positively). It is concluded that multiple and complex intertwined relationships between HPA-axis hyperactivity and systemic immune stimulation participate in the pathophysiology or pathogenesis of major depression.

Adult↗

PubMed1994

Eosinophilic pustular folliculitis and B-cell chronic lymphatic leukaemia.

BACKGROUND: The major problem of eosinophilic pustular folliculitis (EPF) is its generally unknown aetiology. OBJECTIVE AND METHODS: The purpose of this case report is to advise a thorough medical investigation of all patients with EPF. RESULTS: The case of EPF presented seems to be associated with a chronic B-cell lymphatic leukaemia. CONCLUSION: Before regarding EPF as an idiopathic disease of unknown aetiology a thorough immunologic and haematologic investigation has to be advocated.

Eosinophilia↗

PubMed1993

A cohort study of thyroid disease in relation to fallout from nuclear weapons testing.

OBJECTIVE: To estimate individual radiation doses and current thyroid disease status for a previously identified cohort of 4818 schoolchildren potentially exposed to fallout from detonations of nuclear devices at the Nevada Test Site between 1951 and 1958. DESIGN: Cohort analytic study. SETTING: Communities in southwestern Utah, southeastern Nevada, and southeastern Arizona. PARTICIPANTS: Individuals who were still residing in the three-state area (n = 3122) were reexamined in 1985 and 1986, and information on the subjects' and their mothers' milk and vegetable consumption during the fallout period was obtained by telephone interview (n = 3545). After exclusions to eliminate missing data and confounding factors, 2473 subjects were available for analysis. MAIN OUTCOME MEASURES: Individual radiation doses to the thyroid were estimated by combining consumption data with radionuclide deposition rates provided by the US Department of Energy and a survey of milk producers. Relative risk models adjusted for age, sex, and state were fitted using maximum likelihood to period prevalence data for thyroid carcinomas, neoplasms, and nodules. RESULTS: Doses ranged from 0 mGy to 4600 mGy, and averaged 170 mGy in Utah. There was a statistically significant excess of thyroid neoplasms (benign and malignant; n = 19), with an increase in excess relative risk of 0.7% per milligray. A relative risk for thyroid neoplasms of 3.4 was observed among 169 subjects exposed to doses greater than 400 mGy. Positive but nonsignificant dose-response slopes were found for carcinomas and nodules. CONCLUSIONS: Exposure to Nevada Test Site-generated radioiodines was associated with an excess of thyroid neoplasms. The conclusions are limited by the small number of exposed individuals and the low incidence of thyroid neoplasms.

Adolescent↗

PubMed1992

Neutrophil chemotaxis, phagocytosis, and superoxide release in depressive illness.

Recently, some authors have reported defective neutrophil phagocytosis during depression. The present study investigated neutrophil function in 19 healthy controls and in 41 depressed inpatients categorized according to DSM-III into minor, simple major, and melancholic depression. We determined neutrophil function by means of phagocytosis, chemotaxis, and superoxide release. The results show no significant differences in neutrophil function among any of the subtypes of depression and normal volunteers. This suggests that overall neutrophil function is normal during depression. Thus, neutrophils are unlikely to be involved in the increased susceptibility to physical illness of patients with depression.

Adult↗

PubMed1992

A study on the blunted natural killer cell activity in severely depressed patients.

Recently, some investigators have established a blunted natural killer cell activity (NKCA) in severely depressed patients. In order to replicate these findings NKC cytotoxicity assays--on fresh cell suspensions in human plasma and fetal calf serum--were performed in healthy controls and depressed inpatients. Instead of the commonly used 51Cr-release assay we have used a fluorescent NKC cytotoxicity assay, which allows a greater sensitivity. We observed a significantly blunted NKCA in melancholic patients as compared with healthy controls and minor depressives, whilst simple major depressives exhibited an intermediate position. NKC cytotoxicity assays in fetal calf serum were significantly and negatively correlated with the severity of illness. We were unable to establish any relationship between NKCA and measures of hypothalamic-pituitary-adrenal-axis function, such as baseline, postdexamethasone plasma cortisol and 24 hr urinary cortisol secretion. In addition, we did not find any effects of dexamethasone administration (1 mg orally) on NKCA.

Adult↗

PubMed1992

Human retroviruses.

It was only in 1980 that the first human retrovirus, HTLV-1, was isolated. Since then, HTLV-2, HIV-1 and HIV-2 have been identified. All four viruses are transmitted with varying efficiency sexually, vertically from mother to infant, and through blood by transfusion or contamination. HTLV-1 is endemic in populations in south-west Japan, Taiwan, sub-Saharan Africa, the Caribbean, southern USA, central and south America, Australia, Papua New Guinea, Solomon Islands and western Asia. There is now epidemic spread amongst IVDUs in north and south America and southern Europe. HTLV-1 is the aetiological agent of adult T-cell leukaemia/lymphoma (ATL) and tropical spastic paraparesis/HTLV-1 associated myelopathy (TSP/HAM). Other associations which may be causative are with polymyositis, infective dermatitis, gastrointestinal malignant lymphoma and chronic lymphatic leukaemia. ATL appears to be due to malignant transformation of HTLV-1 infected cells, and TSP/HAM to chronic activation of these cells. The epidemiology of HTLV-2 is being separated only recently from HTLV-1 through the application of PCR. It has a low level of endemicity in populations of central Africa, and central and south America. It is being spread epidemically amongst IVDUs in north America and southern Europe. Its association with any pathology in man remains uncertain. HIV-1 is epidemic and spreading rapidly throughout the world. In areas where homosexual contact was the predominant mode of transmission, heterosexual spread is becoming increasingly important. The areas where heterosexual contact is the predominant mode of transmission include the worst affected populations in the world, for example sub-Saharan Africa and some of the Caribbean. There have been recent and explosive increases of HIV-1 seroprevalence in IVDUs and female prostitutes in Asia, especially Thailand and India. Of the diverse pathology following infection, only the haematological consequences are reviewed in detail: these include anaemia, leucopenia, thrombocytopenia, disorders of coagulation and lymphomas. HIV-2, compared to HIV-1, is less infectious and causes less immunosuppression with more slowly progressive disease. It is prevalent in west Africa, but is spreading, albeit slowly, far beyond.

Acquired Immunodeficiency Syndrome↗

PubMed1992

Alpha interferon-2a (Roferon-A) in the treatment of diffuse cutaneous systemic sclerosis: a pilot study. UK Systemic Sclerosis Study Group.

Intramuscular alpha-interferon improved or stabilized skin score in 10/14 (71%) patients with diffuse cutaneous systemic sclerosis. In 64% of patients, their treating physicians rated it as having stabilized or improved the disease. However, it had no significant effect on grip strength, digital contractures, respiratory function or visceral involvement. Type I collagen synthesis was significantly reduced in fibroblasts cultured from clinically 'uninvolved' skin but not in those from lesional skin. Amino-terminal procollagen III peptides in the interferon treated group were not significantly reduced after 6 months of therapy but showed a trend towards stabilization and reduction compared to disease matched controls on no therapy.

Adult↗

PubMed1992

Immune disorders in depression: higher T helper/T suppressor-cytotoxic cell ratio.

This study investigated the leukocyte T helper and T suppressor-cytotoxic cell (sub)set profile of minor, simple major and melancholic depressives versus normal controls. Using both monoclonal antibody staining and flow cytometry, we determined the absolute numbers and percentages of the following T cell immune subsets: T helper (CD4+), T virgin (CD4+CD45+), T memory (CD4+CD45-), T suppressor/cytotoxic (CD8+), CD8+ T suppressor (CD8+CD57-) and CD8+ T cytotoxic (CD8+CD57+) cells. After computing the CD4+/CD8+ ratio, we detected a significantly increased ratio in depressed patients as compared with healthy controls. Depression per se is characterized by a higher percentage of CD4+ and a lower percentage of CD8+CD57- cells. Melancholic depressed subjects exhibit a significantly increased number of CD4+ and CD4+CD45- cells. The combined use of various percentages of CD4+ and CD8+ (sub)sets yields a high degree of marker positivity for melancholia: through cumulative evaluation of those percentages, the marker positivity increases to 68% (sensitivity) and the specificity is 95%. These results together with our previous reports may refer to a depression-related state of T cell activation.

Adult↗

PubMed1992

A canine model for studying laryngospasm and its prevention.

Laryngospasm, if prolonged, can result in serious sequelae due to the lack of a uniformly effective treatment. Prevention, therefore, through pharmacologic intervention, is an attractive concept. In order to study the effects of various drugs in preventing laryngospasm, a reliable animal model capable of producing sequential, repetitive episodes of laryngospasm is necessary. In this study, the canine model of laryngospasm previously described by Aviv, et al. was modified to overcome technical factors which limited its use in this regard. Details of the technique and the results from eight animals will be presented. Results in two animals with the use of prophylactic topical lidocaine will also be discussed. The reliability and reproducibility of this model make it ideal for the study of laryngospasm and open the way for investigation into its prevention.

Administration, Topical↗

PubMed1991

Natural history of thyroid abnormalities: prevalence, incidence, and regression of thyroid diseases in adolescents and young adults.

PURPOSE: This study reports the prevalence, incidence, and regression of thyroid abnormalities in a population observed from adolescence to adulthood. PATIENTS AND METHODS: Examinations for thyroid abnormalities were performed in 4,819 school-age children, ages 11 to 18, in 1965 to 1968; two thirds of this original cohort (3,121) were re-examined 20 years later (1985 to 1986). Each subject with a thyroid abnormality detected by physical examination was studied by means of a series of re-examinations, and tests of thyroid function, imaging, and biopsy to determine the exact nature of the thyroid abnormality. RESULTS: In the initial examinations (1965 to 1968), 185 thyroid abnormalities were found (3.7%). Diffuse hypertrophy with normal function (adolescent goiter) was the most common abnormality (19.3/1,000); 12.7/1,000 had chronic lymphocytic thyroiditis, and 4.6/1,000 had thyroid nodules, including two papillary carcinomas. Hyperthyroidism or hypothyroidism was found in 1.9/1,000. In the follow-up examinations in 1985 to 1986, 298 subjects had thyroid abnormalities (10.5%), of whom 81 (28.7/1,000) had simple goiters, 145 (51.3/1,000) had chronic thyroiditis, 45 (15.9/1,000) had hypothyroidism, 11 (3.9/1,000) had hyperthyroidism, and 66 (23.2/1,000) had nodules, which included 10 carcinomas. Of the 92 subjects with simple or adolescent goiter in 1965 to 1968, 60% were normal by 1985 to 1986, 20% were unchanged, and a few had developed thyroiditis (10%) or colloid goiters (3.0%). Of 61 subjects with thyroiditis, 27% had become normal, 33% remained unchanged, and 33% had become hypothyroid. Of the 22 subjects with thyroid nodules, two had complete disappearance of the nodules, and three had nodules considered to be variants of normal. The others exhibited a variety of nodular pathologic conditions. CONCLUSIONS: The natural history of thyroid disorders, including simple goiter, chronic thyroiditis, hyperthyroidism, hypothyroidism, and nodular diseases of the thyroid, indicates they are dynamic and changeable in form, function, appearance, and disappearance.

Adolescent↗

PubMed1991

Anthropometric and biochemical assessment of the nutritional state in depression: evidence for lower visceral protein plasma levels in depression.

Severe depression is characterized by anorexia and weight loss, symptoms that could endanger the patient's nutritional state. In order to investigate the nutritional state of depressed patients we determined the following in 113 healthy controls and depressed inpatients: (1) anthropometric variables such as body weight, ideal body weight (IBW), percentage of IBW, mean arm circumference, triceps skinfold thickness and arm muscle circumference, and (2) biochemical parameters such as albumin (Alb), prealbumin (Prealb), and transferrin (Tf). We were unable to detect any differences in the anthropometric parameters between healthy controls, minor and major depressed patients. Depressed patients exhibited significantly lower Alb and Tf levels than healthy controls. The drop in both plasma proteins was highly sensitive (72%) and specific (92%) for melancholia. These results may point towards the existence of a disorder in protein homeostasis or protein malnutrition without a marasmic component.

Adult↗

PubMed1990

Leukemia in Utah and radioactive fallout from the Nevada test site. A case-control study.

Previous studies reported an association between leukemia rates and amounts of fallout in southwestern Utah from nuclear tests (1952 to 1958), but individual radiation exposures were unavailable. Therefore, a case-control study with 1177 individuals who died of leukemia and 5330 other deaths (controls) was conducted using estimates of dose to bone marrow computed from fallout deposition rates and subjects' residence locations. A weak association between bone marrow dose and all types of leukemia, all ages, and all time periods after exposure was found. This overall trend was not statistically significant, but significant trends in excess risk were found in subgroups defined by cell type, age, and time after exposure. The greatest excess risk was found in those individuals in the high-dose group with acute leukemia who were younger than 20 years at exposure and who died before 1964. These results are consistent with previous studies and with risk estimates for other populations exposed to radiation.

Acute Disease↗