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Biomedical subjects

J M Crawford

Publications and source records attributed to J M Crawford.

At least 19 recordsLinked to original sources
PubMed1999

Prevalence of chronic respiratory symptoms among Ohio cash grain farmers.

BACKGROUND: The prevalence of chronic cough, chronic phlegm, dyspnea, and non-cold wheeze was estimated from a mixed-mode survey of Ohio cash grain farmers in 1993. METHODS: Personal characteristics of the principal operators (POs) such as age and cigarette smoking, in addition to selected farm characteristics and relevant medical and work history factors potentially associated with both exposure to respiratory irritants and subsequent respiratory symptoms were considered. RESULTS: The overall design-adjusted prevalences (and the corresponding 95% confidence intervals (CIs) were: 9.4% (7.6-11.1%) for chronic cough, 10.8% (9.0-12.6%) for chronic phlegm, 16.2% (14.1-18.3%) for dyspnea, and 8.1% (6.4-9.8%) for non-cold wheeze. In univariate and multivariate analyses, smoking status was found, not surprisingly, to be the strongest predictor of increased symptom prevalence compared to all other factors. Other non-occupational factors found associated with increased symptom prevalence include age (cough, phlegm, dyspnea) and pet allergy (non-cold wheeze). Occupational factors found at least weakly associated with increased symptom prevalence include lifetime hours of cab tractor operation (cough); percent time spent farming (phlegm); having livestock other than cattle, cows, and calves (dyspnea); acres of corn for silage or green chop (cough); acres of alfalfa hay (non-cold wheeze); and personal involvement with pesticides (cough). CONCLUSIONS: Symptom prevalences reported here are consistent with previous findings from studies of other groups of farmers. Results pertaining to factors found associated with symptom prevalences should be interpreted in light of several sources of potential bias.

Adult↗
PubMed1998

Cellularization in Drosophila melanogaster is disrupted by the inhibition of rho activity and the activation of Cdc42 function.

Regulation of cytoskeletal dynamics is essential for cell shape change and morphogenesis. Drosophila melanogaster embryos offer a well-defined system for observing alterations in the cytoskeleton during the process of cellularization, a specialized form of cytokinesis. During cellularization, the actomyosin cytoskeleton forms a hexagonal array and drives invagination of the plasma membrane between the nuclei located at the cortex of the syncytial blastoderm. Rho, Rac, and Cdc42 proteins are members of the Rho subfamily of Ras-related G proteins that are involved in the formation and maintenance of the actin cytoskeleton throughout phylogeny and in D. melanogaster. To investigate how Rho subfamily activity affects the cytoskeleton during cellularization stages, embryos were microinjected with C3 exoenzyme from Clostridium botulinum or with wild-type, constitutively active, or dominant negative versions of Rho, Rac, and Cdc42 proteins. C3 exoenzyme ADP-ribosylates and inactivates Rho with high specificity, whereas constitutively active dominant mutations remain in the activated GTP-bound state to activate downstream effectors. Dominant negative mutations likely inhibit endogenous small G protein activity by sequestering exchange factors. Of the 10 agents microinjected, C3 exoenzyme, constitutively active Cdc42, and dominant negative Rho have a specific and indistinguishable effect: the actomyosin cytoskeleton is disrupted, cellularization halts, and embryogenesis arrests. Time-lapse video records of DIC imaged embryos show that nuclei in injected regions move away from the cortex of the embryo, thereby phenocopying injections of cytochalasin or antimyosin. Rhodamine phalloidin staining reveals that the actin-based hexagonal array normally seen during cellularization is disrupted in a dose-dependent fashion. Additionally, DNA stain reveals that nuclei in the microinjected embryos aggregate in regions that correspond to actin disruption. These embryos halt in cellularization and do not proceed to gastrulation. We conclude that Rho activity and Cdc42 regulation are required for cytoskeletal function in actomyosin-driven furrow canal formation and nuclear positioning.

Animals↗
PubMed1998

Tumor necrosis factor- alpha production to lipopolysaccharide stimulation by donor cells predicts the severity of experimental acute graft-versus-host disease.

Donor T cell responses to host alloantigen are known predictors for graft-versus-host disease (GVHD); however, the effect of donor responsiveness to an inflammatory stimulus such as lipopolysaccharide (LPS) on GVHD severity has not been investigated. To examine this, we used mouse strains that differ in their sensitivity to LPS as donors in an experimental bone marrow transplant (BMT) system. Lethally irradiated (C3FeB6)F1 hosts received BMT from either LPS-sensitive (LPS-s) C3Heb/Fej, or LPS-resistant (LPS-r) C3H/ Hej donors. Mice receiving LPS-r BMT developed significantly less GVHD as measured by mortality and clinical score compared with recipients of LPS-s BMT, a finding that was associated with significant decreases in intestinal histopathology and serum LPS and TNF-alpha levels. When donor T cell responses to host antigens were measured, no differences in proliferation, serum IFN-gamma levels, splenic T cell expansion, or CTL activity were observed after LPS-r or LPS-s BMT. Systemic neutralization of TNF-alpha from day -2 to +6 resulted in decreased intestinal pathology, and serum LPS levels and increased survival after BMT compared with control mice receiving Ig. We conclude that donor resistance to endotoxin reduces the development of acute GVHD by attenuating early intestinal damage mediated by TNFalpha. These data suggest that the responsiveness of donor accessory cells to LPS may be an important risk factor for acute GVHD severity independent of T cell responses to host antigens.

Animals↗
PubMed1998

Host reactive donor T cells are associated with lung injury after experimental allogeneic bone marrow transplantation.

Noninfectious lung injury is common after allogeneic bone marrow transplantation (BMT), but its association with acute graft-versus-host disease (GVHD) is unclear. Using a murine BMT system where donor and host differ by multiple minor histocompatibility (H) antigens, we investigated the nature of lung injury and its relationship both to systemic GVHD and host-reactive donor T cells. Lethally irradiated CBA hosts received syngeneic BMT or allogeneic (B10.BR) T-cell-depleted (TCD) bone marrow (BM) with and without the addition of T cells. Six weeks after BMT, significant pulmonary histopathology was observed in animals receiving allogeneic BMT compared with syngeneic controls. Lung damage was greater in mice that received allogeneic T cells and developed GVHD, but it was also detectable after TCD BMT when signs of clinical and histologic acute GVHD were absent. In each setting, lung injury was associated with significant alterations in pulmonary function. Mature, donor (Vbeta6(+) and Vbeta3(+)) T cells were significantly increased in the broncho-alveolar lavage (BAL) fluid of all allogeneic BMT recipients compared with syngeneic controls, and these cells proliferated and produced interferon-gamma (IFN-gamma) to host antigens in vitro. These in vitro responses correlated with increased IFN-gamma and tumor necrosis factor-alpha (TNF-alpha) in the BAL fluid. We conclude that alloreactive donor lymphocytes are associated with lung injury in this allogeneic BMT model. The expansion of these cells in the BAL fluid and their ability to respond to host antigens even when systemic tolerance has been established (ie, the absence of clinical GVHD) suggest that the lung may serve as a sanctuary site for these host reactive donor T cells. These findings may have important implications with regard to the evaluation and treatment of pulmonary dysfunction after allogeneic BMT even when clinical GVHD is absent.

Animals↗
PubMed1998

Interleukin-11 promotes T cell polarization and prevents acute graft-versus-host disease after allogeneic bone marrow transplantation.

Administration of IL-11 prevented lethal graft-versus-host disease (GVHD) in a murine bone marrow transplant (BMT) model (B6 --> B6D2F1) across MHC and minor H antigen barriers (survival at day 50: 90 vs 20%, P < 0.001). Surpisingly, IL-11 administration polarized the donor T cell cytokine responses to host antigen after BMT with a 50% reduction in IFNgamma and IL-2 secretion and a 10-fold increase in IL-4. This polarization of T cell responses was associated with reduced IFNgamma serum levels and decreased IL-12 production in mixed lymphocyte cultures (MLC). In addition, IL-11 prevented small bowel damage and reduced serum endotoxin levels by 80%. Treatment with IL-11 also reduced TNFalpha serum levels and suppressed TNFalpha secretion by macrophages to LPS stimulation in vitro. IL-11 thus decreased GVHD morbidity and mortality by three mechanisms: (a) polarization of donor T cells; (b) protection of the small bowel; and (c) suppression of inflammatory cytokines such as TNFalpha. We conclude that brief treatment with IL-11 may represent a novel strategy to prevent T cell-mediated inflammatory processes such as GVHD.

Acute Disease↗
PubMed1998

Spectral pathology.

We are investigating the use of optical spectroscopy (fluorescence, reflectance, Raman scattering) for detecting precancerous lesions in the mucosal linings of hollow organs. We present a morphological model for extracting quantitative pathological information from fluorescence spectra, using colonic dysplasia as an example. The potential of this technique in providing histological information in real time without the need for tissue removal is discussed.

Humans↗
PubMed1998

A cross-sectional case control study of work-related injuries among Ohio farmers.

The agricultural industry has consistently been ranked among the most hazardous in the U.S. To date, few analytic studies of occupational injury among farm operators and workers have been conducted. A case control study was undertaken to investigate risk factors for agricultural work-related injury among Ohio farm operators. Cases were selected from among 1,793 respondents to a questionnaire administered during the first phase of the NIOSH-sponsored Ohio Farm Family Health and Hazard Study (OFFHHS). Analysis consisted of description of the injury experience of the sample as a whole, followed by logistic estimation of prevalence odds ratios (pORs) measuring the effect of potential risk factors on injury risk. The case series consisted of 90 white male principal operators (POs) injured doing farm work in the 12 months prior to questionnaire completion. Controls consisted of 1,475 white male POs who reported no injuries. The overall rate of injury was 5 per 100 person-years. The most notable result is the relationship between self-reported neurotoxic symptoms and injury, suggesting those with more reported symptoms were at greater risk of injury. The crude OR, when compared to the reference score of < or = 27, increased from 1.74 (95% CI = 0.60-5.09) in the 28-30 category, to 1.89 (95% CI = 0.71-5.03) in the 31-35 category, to 2.96 (95% CI = 1.10-7.96) in the highest category of test score. The P value for trend was 0.0218. These associations largely persisted after controlling for potential confounders with multiple logistic regression. Risk was inversely related to age. The results show marked increases in risk of injury associated with farmers younger than 30 and increased severity of self-reported neurological symptoms, controlling for potential confounding.

Accidents, Occupational↗
PubMed1998

Enhanced Na+-dependent bile salt uptake by WIF-B cells, a rat hepatoma hybrid cell line, following growth in the presence of a physiological bile salt.

Although bile salts are toxic to the liver at high plasma concentrations, the effects of physiological concentrations of bile salts on normal hepatic function are poorly understood. We examined the effect of taurocholate (TC) on the basolateral uptake of [3H]TC in WIF-B cells, a hybrid cell line stably exhibiting in vitro the structural and functional polarity of hepatocytes. Cells were grown in the absence or presence of TC (50 micromol/L) over 12 days, and then incubated with [3H]TC concentrations ranging from 1 to 250 micromol/L. For both control and TC-grown cells, uptake of [3H]TC was linear over 2 minutes. In control cells, the Km for [3H]TC Na+-dependent uptake over 1 minute was 6 +/- 5 micromol/L, and the Vmax was 45 +/- 6 pmol TC/mg protein/min (+/- SEM). TC-grown cells exhibited no significant change in Km but showed a doubling of Vmax to 87 +/- 6 pmol TC/mg protein/min (P < .005). In both control and TC-grown cells, maximal uptake of [3H]TC occurred following 10 to 12 days in culture, with TC-grown cells consistently showing greater rates of [3H]TC uptake from 4 to 14 days in culture. Western blots immunostained for the basolateral Na+-dependent plasma membrane protein, ntcp, revealed the appropriate approximately 50-kd band in control and TC-grown cells, and confocal immunofluorescence microscopy demonstrated staining along the basolateral plasma membrane. Northern blots hybridized with a cDNA probe directed against ntcp indicated a modest TC-induced increase in mRNA levels. Reverse-transcriptase polymerase chain reaction (RT-PCR) using RNA isolated from WIF-B cells and oligonucleotide primers specific for rat ntcp or human NTCP transcripts revealed only the presence of the rat ntcp transcript. We conclude that bile salts, at concentrations normally found in mammalian portal blood, may be capable of promoting enhanced hepatocellular bile salt uptake via an increase in basolateral Na+-dependent plasma membrane transport capacity.

Animals↗
PubMed1998

The normal adult human liver biopsy: a quantitative reference standard.

In assessing adult human liver histology, questions remain concerning the normal number of portal tracts and bile ducts in a liver biopsy. We therefore reviewed liver biopsies obtained with use of a percutaneous Menghini cutting needle (14G, internal diameter 1.6 mm), from 16 patients undergoing liver biopsy for screening procedures (age 49 +/- 14 years, +/-SD) and found to be normal by histological examination. The average aggregate length of the liver tissue was 1.8 +/- 0.8 cm (area of 16.4 +/- 10.7 mm2), representing 7 +/- 3 tissue fragments. Portal triads containing at least one profile each of a portal vein, hepatic artery, and interlobular bile duct numbered 11 +/- 6 per biopsy (range 3-23). Portal dyads, which did not contain one of these profiles, usually the portal vein, numbered 8 +/- 5 (range 1-18). On a per-specimen basis, 38% of portal tracts did not contain a portal vein, 7% did not contain a bile duct, and 9% did not contain a hepatic artery. Because of multiplicity of profiles within portal tracts, however, the average number of profiles per portal tract was 6 +/- 5 (range 2-35). Notably, on average there were 2.3 +/- 2.2 interlobular bile ducts per portal tract, compared to 2.6 +/- 2.3 hepatic arteries and 0.7 +/- 0.7 portal veins. The average minimum external diameter of interlobular bile ducts was 13 +/- 4 microm, of hepatic arteries 12 +/- 5 microm, and of portal veins 35 +/- 25 microm. Bile ducts greater than 30 microm in diameter were rare, only one each in two biopsies were observed. In contrast, probable canals of Hering were occasionally evident at the periphery of portal tracts (6 +/- 6 per biopsy) and within the lobular parenchyma as strings of cuboidal cells (5 +/- 5 per biopsy). We conclude that, although multiplicity of profiles is normal, portal dyads are almost as common as portal triads in normal peripheral liver tissue. On average, there are two interlobular bile ducts, two hepatic arteries, and one portal vein per portal tract, with 6 full portal triads per linear cm of tissue obtained by external Menghini biopsy technique with use of a 14G needle, equivalent to 0.8 +/- 0.5 portal triads per mm2. By serving as a reference standard for adult human liver histology, these findings may assist in the histopathological assessment of liver biopsies, particularly those performed for disease conditions featuring loss of intrahepatic bile ducts.

Adult↗
PubMed1997

Hepatic secretion of phospholipid vesicles in the mouse critically depends on mdr2 or MDR3 P-glycoprotein expression. Visualization by electron microscopy.

Hepatocellular secretion of bile salts into the biliary space induces phospholipid and cholesterol secretion, but the mechanism for integrated lipid secretion is poorly understood. Knockout mice unable to make the canalicular membrane mdr2 P-glycoprotein exhibit normal rates of bile salt secretion, yet are virtually incapable of secreting biliary phospholipid and cholesterol. As the mdr2 P-glycoprotein is thought to mediate transmembrane movement of phospholipid molecules, this mouse model was used to examine the mechanism for biliary phospholipid secretion. In wild-type mdr2 (+/+) mice, ultrarapid cryofixation of livers in situ revealed abundant unilamellar lipid vesicles within bile canalicular lumina. Although 74% of vesicles were adherent to the external aspect of the canalicular plasma membrane, bilayer exocytosis was not observed. Vesicle numbers in mdr2 (+/-) and (-/-) mice were 55 and 12% of wild-type levels, respectively. In a strain of mdr2 (-/-) mice which had been "rescued" by heterozygous genomic insertion of the MDR3 gene, the human homologue of the murine mdr2 gene, vesicle numbers returned to 95% of wild-type levels. Our findings indicate that biliary phospholipid is secreted as vesicles by a process largely dependent on the action of the murine mdr2 P-glycoprotein or human MDR3 P-glycoprotein. We conclude that mdr2-mediated phospholipid translocation from the internal to external hemileaflet of the canalicular membrane permits exovesiculation of the external hemileaflet, a vesiculation process promoted by the detergent environment of the bile canalicular lumen.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed1997

Total body irradiation and acute graft-versus-host disease: the role of gastrointestinal damage and inflammatory cytokines.

The influence of bone marrow transplantation (BMT) conditioning regimens on the incidence and severity of graft-versus-host disease (GVHD) has been suggested in clinical BMT. Using murine BMT models, we show here an increase in GVHD severity in several donor-recipient strain combinations after intensification of the conditioning regimen by increasing the total body irradiation (TBI) dose from 900 cGy to 1,300 cGy. Increased GVHD was mediated by systemic increases in tumor necrosis factor alpha (TNF alpha). Histologic analysis of gastrointestinal tracts showed synergistic damage by increased TBI and allogeneic donor cells that permitted increased translocation of lipopolysacharide (LPS) into the systemic circulation. In vitro, LPS triggered excess TNF alpha from macrophages primed by the GVH reaction. In addition, macrophages isolated within 4 hours of conditioning were primed in proportion to the TBI dose itself to secrete TNF alpha. Thus, the higher TBI dose increased macrophage priming and increased gut damage after allogeneic BMT, causing higher systemic levels of inflammatory cytokines and subsequent severe GVHD. These data highlight the importance of conditioning in GVHD pathophysiology and suggest that interventions to prevent LPS stimulation of primed macrophages may limit the severity of GVHD after intensive conditioning for allogeneic BMT.

Animals↗
PubMed1997

A longitudinal study of unsaturated iron-binding capacity and lactoferrin in unstimulated parotid saliva.

Availability of iron is one important nutritional parameter for microbial growth in saliva. This longitudinal study measured the diurnal and day-to-day variations in the total iron (TI), total iron-binding capacity (TIBC), unsaturated iron-binding capacity (UIBC), and lactoferrin (LF) in unstimulated human parotid saliva. Saliva was collected from 15 young male subjects in the morning and afternoon hours each day for five consecutive days. The TI and TIBC were determined by flameless atomic absorption spectroscopy, and UIBC was determined by subtraction of TI from TIBC. The LF was determined by "sandwich" enzyme-linked immunosorbent assay (ELISA). One peripheral blood sample of each subject was also analyzed for TI, TIBC, and ferritin. The results showed no significant diurnal or day-to-day variation of TI, TIBC, UIBC, or LF in saliva for most subjects. However, significant between-subject variations were observed for most parameters. Variations ranged from subjects with constantly positive UIBC values to subjects with constantly negative UIBC values. The relationship between the LF values and the TI and TIBC values suggests that other iron-binding protein(s) are present in saliva. Also, saliva had significantly lower TIBC values than serum. This finding indicated that iron may be easily available in saliva. However, further studies are required to determine the relationship between UIBC value of saliva and oral and dental diseases, and also to detect the presence of other iron-binding proteins in saliva.

Adult↗
PubMed1997

Evolution of H5 subtype avian influenza A viruses in North America.

The phylogenetic relationships of the hemagglutinin (HA) and non-structural (NS) genes from avian influenza (AI) H5 subtype viruses of North American origin are presented. Analysis of the HA genes of several previously uncharacterized isolates from waterfowl and turkeys provided clear evidence of significant sequence variation and existence of multiple virus clades or sub-lineages, maintained in migratory waterfowl. Phylogenetic analysis of NS gene sequences further demonstrated multiple sub-lineages and also demonstrated re-assortment of two NS alleles in wild duck populations. Based on currently available HA1 gene sequences, at least four clades exist with waterfowl isolates included in three of the four groups. The most genetically unstable of these sub-lineages is composed of recent poultry isolates from the outbreak of AI in Central Mexico. This group of viruses, which replicated unabated in chickens for at least 16 months, exhibited an increased rate of mutation in both the HA and NS gene. Comparison of the HA1 sequence data for all available North American H5 subtype viruses demonstrated minimal variation both in and around the amino acids predicted to be involved in the HA receptor binding site. The sequences also revealed that migratory waterfowl, live poultry market chicken, and turkey isolates uniformly lack a glycosylation site at amino acid 236 in the HA protein which is present in commercial chicken isolates.

Animals↗
PubMed1997

Mixed-mode survey of female veterinarians yields high response rate.

In a recent study of female veterinarians, a subgroup of health professionals growing rapidly in number, the authors employed a mixed-mode survey design in targeting the cohort of women graduating from all US veterinary colleges during the 11-year period 1970-80 (n = 2,997). The questionnaire elicited information on a variety of health and occupational factors and required 35 minutes on average to complete. In the first stage, a modified version of Dillman's Total Design Method for mailed, self-administered questionnaires was employed, yielding a response rate of 82.9%. In the second stage, a telephone interview of all mail non-respondents was attempted, yielding a response rate here of only 30.1%, but increasing the overall response rate among those contacted to 90.2%. Non-respondents differed little from mail (early) or telephone (late) respondents with respect to year of graduation and geographic region of veterinary college attendance. Gentle probing of telephone non-respondents suggested the personal nature of some questions and the amount of time required to answer all questions were the main reasons they chose not to participate. It therefore appears that conventional survey techniques may be successfully employed in health studies of health professionals, particularly if issues of great concern to the target population are addressed.

Bias↗