Search PubMed⌕ Search

Biomedical subjects

J R Davis

Publications and source records attributed to J R Davis.

At least 163 records · Page 9Linked to original sources

Characterization of Epstein-Barr virus-induced lymphoproliferation derived from human peripheral blood mononuclear cells transferred to severe combined immunodeficient mice.

Mice with severe combined immunodeficiency (SCID) received 6 X 10(7) fresh human peripheral blood mononuclear cells (PBMC) intraperitoneally from Epstein-Barr virus (EBV)-seropositive and -seronegative donors. B95-8 EBV was inoculated intraperitoneally and intravenously to the mice 6 weeks after transfer of seronegative PBMC. Three of four mice transferred with PBMC from two EBV-seropositive donors and two of four mice from two EBV-seronegative donors inoculated with EBV developed fatal EBV-induced lymphoproliferative disease within 6 to 10 weeks. These tumors were oligoclonal or polyclonal by cytoplasmic immunoglobulin expression. Furthermore no consistent clonal chromosomal abnormalities were shown. Cell lines established from these tumors showed low cloning efficiency in soft agarose. In addition, latent membrane protein, B-lymphocyte activation antigen (CD23), and cell-adhesion molecules (ICAM-1, CD18) all were expressed in the EBV-positive infiltrating lymphoproliferative lesions in each mouse. These results suggest that lymphoid tumors are comparable to lymphoblastoid cell lines immortalized by EBV and are not malignant lymphomas such as Burkitt's lymphoma. This model may be useful for investigating mechanisms responsible for the growing numbers of lymphoproliferative diseases that are occurring in patients with inherited or acquired immunodeficiencies.

Animals↗

Human studies with synthetic peptide sporozoite vaccine (NANP)3-TT and immunization with irradiated sporozoites.

The synthetic peptide Plasmodium falciparum circumsporozoite (CS) protein conjugate vaccine (NANP)3-TT was safe when given parenterally to 202 volunteers. However, with a few notable exceptions, antibody responses were low and could not be boosted. Vaccinees' lymphocytes did not proliferate when exposed in vitro to (NANP)3. The tetanus toxoid (TT) carrier immunomodulated the response to the CS peptide in that both epitopic suppression and immune enhancement were demonstrated during the course of the clinical trials. During efficacy challenge studies, 1 of 7 vaccinees was protected against sporozoite challenge and in other vaccinees the prepatent period was significantly delayed. P. falciparum-infected mosquitos were irradiated with 20,000 rad (200 Gy). Five volunteers were immunized with 54, 55, 224, 663, and 715 total infective bites of irradiated mosquitos in an attempt to immunize with attenuated sporozoites. Four of these volunteers had significant humoral and cellular immune responses. Two volunteers (who received the largest immunizing doses) were challenged by the bites of infective mosquitos and both developed parasitaemia. In the volunteer with the highest antibody titre there was a marked delay in patency as determined by serial plasmodial cultures. T-cell clones are being obtained and characterized.

Adult↗

Efforts in primary-care practice to control tobacco use.

In this article, the authors findings lead them to conclude that because of the devastating effects of smoking on health, the public could experience widespread health benefits if primary care physicians became more active in encouraging patients to stop smoking.

Allied Health Personnel↗

Cancer control and public health in Missouri: a time for action.

National reports on cancer mortality now show that most cancer deaths are preventable. The recent national focus on prevention of such chronic diseases may indicate that public health departments need to consider a shift in emphasis from infectious to chronic disease control.

Humans↗

Racial differences in cancer mortality in Missouri.

The discrepancy between black and white cancer mortality rates remains a cause of concern for the public health community. The authors discuss some of the factors that contribute to the problem and suggest that an organized local, state and national effort is necessary to find a solution.

Adult↗

Giant invasive prolactinoma: a case report and review of nine further cases.

Very large prolactinomas are rare and may be difficult to treat. We present the report of a patient with an exceptionally aggressive tumour which extended outside the skull and emerged within the internal jugular vein. Bromocriptine induced only transient suppression of serum prolactin. In vitro studies of tissue from this prolactinoma showed that although prolactin secretion was reduced by both bromocriptine and dopamine, neither agent affected cytoplasmic levels of prolactin mRNA, suggesting relative autonomy of prolactin synthesis. We reviewed the progress of nine other patients with very large prolactinomas and serum prolactin levels greater than 100,000 mU/l. In three cases, treatment with bromocriptine rapidly reduced tumour size and serum prolactin levels became normal, but in the other cases responses were slower and less marked. Substantial amounts of residual pituitary tumour were seen in all cases where serum prolactin remained above 1000 mU/l, but also in one case where serum prolactin returned to normal, showing that serum prolactin levels are not reliable indicators of tumour size. Two patients died: one developed a CSF leak, and one pneumococcal meningitis in the absence of recognized CSF leakage. This emphasizes the significant morbidity associated with very large prolactinomas. The ideal long-term treatment of these tumours remains uncertain, but bromocriptine therapy alone is often inadequate. Cases of apparent bromocriptine resistance may reflect abnormal regulation of prolactin gene expression.

Adult↗

Cancer risks among Missouri farmers.

A series of case-control studies was conducted to investigate cancer risks among farmers. These studies were based on Missouri Cancer Registry data for 15,000 white male patients, including 1720 subjects classified as farmers, registered between 1984 and 1988. For each cancer site, all other cancer registrations formed the control group. The largest risks among farmers were found for lip cancer (odds ratio [OR], 3.07; 95% confidence interval [CI], 1.99 to 4.73) and cancer of the bone (OR, 2.02; 95% CI, 0.66 to 5.81). Elevated risks were observed for several other sites, including the nasal cavity and sinuses (OR, 1.66; 95% CI, 0.54 to 4.70), prostate (OR, 1.33; 95% CI, 1.18 to 1.51), non-Hodgkin's lymphoma (OR, 1.40; 95% CI, 1.04 to 1.85), and multiple myeloma (OR, 1.40; 95% CI, 0.87 to 2.24). Other smaller elevations in risk were noticed for cancer of the rectum (OR, 1.21; 95% CI, 0.95 to 1.53), liver (OR, 1.19; 95% CI, 0.58 to 2.37), malignant melanoma (OR, 1.26; 95% CI, 0.63 to 2.45), kidney (OR, 1.21; 95% CI, 0.89 to 1.65), and leukemia (OR, 1.12; 95% CI, 0.81 to 1.55); however, some of these estimates were imprecise due to small numbers. The overall OR for lymphatic and hematopoietic cancers was 1.28 (95% CI, 1.06 to 1.56). Consistent with previous studies, a decreased risk of lung cancer was observed among farmers (OR, 0.67; 95% CI, 0.60 to 0.76). The current findings are presented in the context of other recent studies, including discussions of possible causes of farming-associated excess cancer risk and possible sources of bias.

Adult↗

Study of lung cancer histologic types, occupation, and smoking in Missouri.

A case-control study of lung cancer was conducted to evaluate the relationship between lung cancer histologic types and occupation, adjusted for smoking. A total of 4,431 white male cases and 11,326 cancer controls, diagnosed between 1980 and 1985, were identified through the Missouri Cancer Registry. For all histologic types combined, excess risk was observed among many a priori suspected high-risk occupations. Lung cancer was elevated among men employed as insulators (odds ratio [OR] = 6.0; 95% confidence interval [CI] = 0.7, 137.8), carpenters (OR = 1.3; 95% CI = 1.0, 1.7), painters, plasterers, and wallpaper hangers (OR = 2.0; 95% CI = 1.2,3.3), structural metal workers (OR = 1.9; 95% CI = 0.6,6.0), mechanics and repairers (OR = 1.3; 95% CI = 1.0,1.7), motor vehicle drivers (OR = 1.5; 95% CI = 1.2,1.8), police and firefighters (OR = 1.6; 95% CI = 1.1,2.3), and food service personnel (OR = 1.8; 95% CI = 1.0,3.5). A deficit of lung cancer was observed among farmers (OR = 0.9; 95% CI = 0.7,1.0). Adenocarcinoma of the lung was elevated among carpenters (OR = 1.6; 95% CI = 1.0,2.5) and cabinet and furniture makers (OR = 2.0; 95% CI = 0.4,8.1), which is interesting because of the previous reports of excess adenocarcinoma of the nasal cavity associated with wood dust exposure. Adenocarcinomas were also elevated among plumbers (OR = 2.0; 95% CI = 1.0,3.8) and printers (OR = 1.8; 95% CI = 0.7,4.2). Electricians were at slightly increased risk for adenocarcinoma (OR = 1.5; 95% CI = 0.7,2.8) and "other" or mixed cell types of lung cancer (OR = 1.5; 95% CI = 0.8,2.9) but at decreased risk for small cell (OR = 0.8; 95% CI = 0.3,2.0) and squamous cell (OR = 0.8; 95% CI = 0.4,1.6) tumors. Among welders, adenocarcinoma (OR = 1.7; 95% CI = 0.7,3.8) and squamous cell (OR = 1.7; 95% CI = 0.9,3.3) cancers were elevated, but small cell and "other" lung cancers were not. Despite the limitations of the Cancer Registry data, some interesting associations were observed that merit further study, particularly the association between lung adenocarcinoma and occupational exposure to wood and wood dust.

Adenocarcinoma↗

Interferon-gamma in a family with X-linked lymphoproliferative syndrome with acute Epstein-Barr virus infection.

A 20-month-old male with fulminant infectious mononucleosis and the X-linked lymphoproliferative syndrome (XLP) was studied. Epstein-Barr virus (EBV)-determined nuclear antigen (EBNA) and EBV DNA were detected in various tissues. Despite a combined treatment with acyclovir, immunoglobulin, and methylprednisolone, the patient deteriorated rapidly. Following treatment with recombinant interferon-gamma (IFN-gamma), defervescence occurred and circulating EBNA-positive cells markedly decreased. IFN-gamma prior to treatment ranged from 10.8 to 24.5 U/ml in the patient's serum and increased linearly post exogenous IFN-gamma treatment. His natural killer (NK)-cell activity remained in the normal range throughout his illness but autologous EBV-infected cells were not killed in vitro by his peripheral blood lymphocytes (PBL). These results suggest that patients with the fatal infectious mononucleosis phenotype of XLP may produce endogenous IFN-gamma. Defective cytotoxic T cells against EBV-infected cells seem to be responsible for the fulminant infectious mononucleosis in this patient.

Acute Disease↗

DNA ploidy, grade, and stage in prognosis of uterine cervical cancer.

A retrospective study of 56 cases of uterine cervical squamous carcinoma evaluated DNA content, histological grade, and clinical stage as indicators of prognosis. Minimum survivor follow-up was 24 months. Following standard radiation therapy, there were 40 cures and 16 treatment failures. DNA content was measured by flow cytometry of pretreatment biopsies removed from paraffin. There were 18 diploid cases and 38 aneuploid (67.9%). Aneuploid cases included 6 with very high G2-M peaks (greater than or equal to 15% of the cell sample). DNA ploidy correlation with prognosis was not statistically significant. However, both grading by a multiple parameter method (P less than 0.0133) and staging (P less than 0.0064) were significant prognostic factors. Higher grade and stage correlated with treatment failure.

Adult↗

A study of the accuracy of cancer risk factor information reported to a central registry compared with that obtained by interview.

Sources of readily available data for cancer surveillance are frequently sought. To assess the validity of information on cancer risk factors that is routinely collected in conjunction with cancer incidence reporting, the authors completed interviews for 441 patients identified through the Missouri Cancer Registry from June 1986 to May 1987. Interviews elicited information on employment history, smoking, and alcohol consumption. Data collected from interviews were compared with those previously reported to the Registry by participating hospitals. Exact agreements of three-digit US Census codes were 70% for occupation and 72% for industry. Concordance for never- versus ever-smoking status was 83%, and a high correlation (r = 0.93) was observed for level of smoking. Agreement on alcohol consumption was lower (65%), largely because of the presence of false negatives. Misclassification occurred in a random manner for occupational variables; however, differential misclassification was present for smoking and alcohol histories. Despite the limitations of registry-collected data, these findings suggest that cancer registries that obtain information on cancer risk factors may be suitable for exploratory studies, especially those involving occupational cancer surveillance.

Adult↗

Comparison of different dose regimes of aminohydroxypropylidene-1,1-bisphosphonate (APD) in hypercalcaemia of malignancy.

1. The new intravenous bisphosphonate drug aminohydroxypropylidine bisphosphonate (APD) is effective in treating the hypercalcaemia of malignant disease, but the optimum dose regimen is not yet established. We have treated twenty-seven patients with malignant hypercalcaemia (corrected calcium greater than 3.00 mmol l-1) with intravenous APD, comparing three regimens of drug administration. 2. Patients were randomly allocated to receive a single dose of APD 30 mg on day 1 (group A, n = 9), two consecutive doses of 30 mg on days 1 and 2 (group B, n = 9) or a single 60 mg dose on day 1 (group C, n = 9). The patients were severely hypercalcaemic, and in nine (33%) the corrected serum calcium was higher than 4.00 mmol l-1 and all were severely ill: three patients died within 48 h of receiving the initial dose and seven died within the first week. 3. Serum calcium levels fell by day 7 in all patients: in group A, from 3.91 +/- 0.40 (s.d.) mmol l-1 to 2.91 +/- 0.49; in group B, from 3.59 +/- 0.33 to 2.63 +/- 0.23 mmol l-1; and in group C, from 3.71 +/- 0.43 to 2.66 +/- 0.39 mmol l-1. Complete response, defined by a nadir calcium (on days 5-12) below 2.60 mmol l-1 occurred in eleven of 24 surviving patients (4/9 in group A, 4/7 in group B, and 3/8 in group C). The remaining patients showed a partial response with serum calcium falling at least 0.25 mmol l-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Evidence for a 6.5-day minimum exoerythrocytic cycle for Plasmodium falciparum in humans and confirmation that immunization with a synthetic peptide representative of a region of the circumsporozoite protein retards infection.

Immunization with a synthetic peptide which is representative of part of the repeating region of Plasmodium falciparum circumsporozoite protein resulted in an immunity which allowed vaccinees to retard the development of patent malaria as compared to nonimmunized controls. Analysis of infection dynamics showed that immunity could be attributed to either neutralization of about 92% of inoculated sporozoites, delayed development of the majority of parasites, or a combination of neutralization and delayed development. In spite of this impressive antiplasmodial capacity, all volunteers after being bitten by infected mosquitoes developed malaria, and seven of eight developed parasitemia between 6.5 and 7.0 days after infective mosquito bites.

Animals↗

Regulation of growth hormone secretion and messenger ribonucleic acid accumulation in human somatotropinoma cells in vitro.

GH secretion and mRNA levels were measured in cultured cells obtained from six human pituitary somatotroph tumors to investigate their hormonal and intracellular regulation. The responses were variable between tumors, but, in general, mRNA levels were less responsive than GH release to in vitro manipulation. GH-releasing factor [GRF-(1-29) amide; 10 nM] increased GH release and mRNA levels in three of four tumors tested to 30-97% above control values, but the fourth tumor was unresponsive. Somatostatin (1 microM) inhibited GH release significantly in four of the six cases, to 35-79% of control levels, but had no inhibitory effect on GH mRNA accumulation, in contrast to earlier studies on rat pituitary tissue. Bromocriptine (100 nM) likewise inhibited GH release (50-75% of control), but not GH mRNA levels, in the four tumors tested. Forskolin (10 microM; used to activate adenylate cyclase) stimulated GH release and mRNA levels in the two cases that responded most clearly to GRF, but had no significant effect in the other tumors; however, the phorbol ester 12-O-tetradecanoyl phorbol-13-acetate (100 nM) had no consistent effect on mRNA levels despite stimulating secretion in four of six cases. Thus, there was considerable variation in responses among the tumors tested; however, the responsiveness to GRF was approximately paralleled by that to forskolin, consistent with the suggestion that adenylate cyclase activity and responsiveness are variable among these tumors. Furthermore, the divergent effects of somatostatin on GH release and mRNA suggest uncoupling between its receptor and transcriptional regulatory mechanisms.

Adenoma↗

Suppression of prolactin release and mRNA accumulation by two novel dopamine agonist agents.

Two novel dopamine agonist drugs, CV 205-502 and CQP 201-403, have been investigated to compare their effects on prolactin secretion and prolactin mRNA accumulation in cultured rat pituitary cells. Both drugs gave dose-dependent suppression of prolactin release over a 24 h incubation period: when each drug was used at 100 nmol/l CV 205-502 and CQP 201-403 induced suppression to 8.9 +/- 1.7 and 10.2 +/- 1.8% of control release, respectively, compared to 26.7 +/- 4.8% of control with 100 nmol/l bromocriptine. There was no consistent effect on growth hormone release. Cytoplasmic accumulation of prolactin mRNA was also inhibited by both drugs at this concentration, to 50.2 +/- 5.5% of control values by CV 205-502 and to 67.4 +/- 8% of control by CQP 201-403, and to a similar extent by 100 nmol/l bromocriptine (50.6 +/- 9.1% of control). None of the drugs had any significant effect on GH mRNA levels. These data suggest that the agents exert their effect at a pretranslational stage of prolactin synthesis, as well as at the level of hormone release.

Aminoquinolines↗

Estimate of Plasmodium falciparum sporozoite content of Anopheles stephensi used to challenge human volunteers.

Plasmodium falciparum infected Anopheles stephensi, taken from a group of mosquitoes which had been used to challenge recipients of (NANP)3-TT vaccine, were tested for P. falciparum sporozoite content by an immunoradiometric assay. Seventy-six percent were infected with mean and median sporozoite equivalents per mosquito of 220,994 and 217,398, respectively (SD = 54,911). This sporozoite density is greater than that usually found in the field. These data suggest that this challenge for evaluating P. falciparum sporozoite vaccines is a demanding test of immunity.

Animals↗