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PubMed1999

RET: a poly A-trap retrovirus vector for reversible disruption and expression monitoring of genes in living cells.

Gene trapping is a form of insertional mutagenesis that causes disruption of gene function. Here we report the construction and extensive examination of a versatile retrovirus vector, RET (removable exon trap). The RET vector uses an improved poly A-trap strategy for the efficient identification of functional genes regardless of their expression status in target cells. A combination of a potentially very strong splice acceptor and an effective polyadenylation signal assures the complete disruption of the function of trapped genes. Inclusion of a promoterless GFP cDNA in the RET vector allows the expression pattern of the trapped gene to be easily monitored in living cells. Finally, because of loxP-containing LTRs at both ends, the integrated proviruses can be removed from the genome of infected cells by Cre-mediated homologous recombination. Hence, it is possible to attribute the mutant phenotype of gene-trapped cells directly to RET integration by inducing phenotypic reversion after provirus excision. The RET system can be used in conjunction with cell lines with functional heterozygosity, embryonic stem cells, lineage-committed cell lines that differentiate in response to specific inducing factors and other responsive cell lines that can be selected by virtue of their induced green fluorescence protein expression.

3T3 Cells↗

PubMed2003

Cloning, characterization, and developmental expression of a putative farnesoic acid O-methyl transferase in the female edible crab Cancer pagurus.

Farnesoic acid methyl transferase (FAMTase) catalyzes methylation of farnesoic acid to yield the crustacean juvenoid, methyl farnesoate (MF). A full-length cDNA encoding a 275 amino acid putative FAMTase has been isolated from the mandibular organ of the female edible crab (Cancer pagurus) by reverse transcriptase-polymerase chain reaction in conjunction with cDNA library screening. A high degree of sequence identity was found between this and other putative crustacean FAMTases. Conceptual translation and protein sequence analysis suggested that phosphorylation could occur at multiple sites in the FAMTase. This finding is consistent with the recent observation that endogenous FAMTase activity in mandibular organ extracts can be regulated by phosphorylation in vitro. We demonstrated that the recombinant FAMTase could be expressed as a LacZ-fusion protein in Escherichia coli and have undertaken its partial purification from inclusion bodies. In an established assay system, the recombinant FAMTase lacked activity. Northern blotting demonstrated widespread expression of an approximately 1250-nucleotide FAMTase transcript in female C. pagurus tissues. Levels of FAMTase transcripts in mandibular organs of female C. pagurus were found to fluctuate during vitellogenesis and embryonic development. Throughout the spring of 2002, an HPLC-based method was used to measure hemolymph MF titers in more than 70 female specimens of C. pagurus, which segregated into "high MF" and "low MF" groups. The high MF titers, which occurred before or during early vitellogenesis, coincided with, or were preceded by, elevated levels of putative FAMTase mRNA in the mandibular organs.

Amino Acid Sequence↗

PubMed1990

[Viral diseases of the outer eye--rapid diagnosis by immunohistochemistry].

Rapid diagnosis of viral diseases of the outer eye was attempted by means of immunohistochemical methods. Specimens were obtained with a nitrocellulose membrane, used as a blotter of immunoblotting test. An impression of the corneal or conjunctival surface was obtained by anesthetizing the eye and lightly pressing the membrane against the tissues. In some cases, scraping materials were taken on a slide glass. Viral antigens in the specimens were detected by peroxidase-antiperoxidase (PAP) method, ABC system (Vectastain), or immunofluorescence. Four common diseases were studied. Dendritic corneal lesions caused by herpes simplex virus (HSV) were impressed on the membrane, and exhibited exact duplicates of lesions which were composed of PAP-positive epithelial cells. Under a high magnification, pathologic changes such as margination of chromatin, intranuclear inclusion bodies, and multinucleated giant cells were observed. Of 27 cases of epithelial herpetic keratitis, 25 showed positive results. The impression can permit examination of a minute lesion, therefore, is superior to scraping. Dendritic lesions caused by varicella-zoster virus (VZV) have a characteristic morphology different from those of HSV. Impressions showed the virus antigen, when treated with fluorescein-labeled anti-VZV monoclonal antibody. Appearance of such a dendrite in disorders of unknown cause indicates the etiology. Conjunctival impressions of adenovirus (Adv) conjunctivitis examined by the PAP method revealed Adv-antigen containing cells. Of 64 cases analyzed, 24 PAP-positive cases were compared with the 35 culture-proven cases. The sensitivity of PAP method was 69%, and the specificity was 97%. The detection rate varied according to serotype, and was especially low (33%) in type 3. Guinea pig antisera with high titers against enterovirus type 70 (EV70) and a variant of coxsackievirus A type 24 (CA24v), the causative viruses of acute hemorrhagic conjunctivitis (AHC), were obtained. Using these sera as the primary antibody, the antigen of each virus was localized in the cytoplasm of infected HeLa cells by either ABC, or immunofluorescence. Conjunctival cells from patients with EV70 AHC were antigen-positive for 3 days after the onset of disease. Though epidemics of CA24v AHC have only been experienced in Okinawa, sporadic cases have been observed in other districts of Japan.

Adenovirus Infections, Human↗

PubMed1994

[Chronic unilateral keratoconjunctivitis in molluscum contagiosum of the upper eyelid margin].

PATIENT AND METHODS: Over a period of one year a 33-year-old married housewife, mother of two healthy children, complained of an initially recurrent, in the last 6 months persisting conjunctivitis, upper and lower lid edema, dacryorrhea and photophobia concerning the left eye. Neither topical derivates of cromoglycin acid, antibiotics nor steroids brought relief. Half a year ago the patient had noticed a "little nodule" of the lateral upper eyelid without tendency to grow. The visual acuity was 0.8 due to a punctate superficial keratopathy. In addition a marked follicular conjunctivitis was present. Our examination revealed a little whitish-rosy tumor with elevated edges and a central crater at the lateral margin of the upper lid. The right eye was completely normal. The tumor was totally excised preserving the lid margin. Our histopathological diagnosis was "molluscum contagiosum". Four weeks after surgery the keratoconjunctivitis had subsided without further medication. CONCLUSION: In persisting unilateral conjunctivitis without amelioration after any topical therapy the eyelids should be checked carefully for a tumor to be excised. In older patients a sebaceous gland carcinoma must be ruled out. Considering the patient's personal history a chlamydial infection should be kept in mind as a differential diagnosis.

Adult↗

PubMed2000

Syntactic structure assembly in human parsing: a computational model based on competitive inhibition and a lexicalist grammar.

We present the design, implementation and simulation results of a psycholinguistic model of human syntactic processing that meets major empirical criteria. The parser operates in conjunction with a lexicalist grammar and is driven by syntactic information associated with heads of phrases. The dynamics of the model are based on competition by lateral inhibition ('competitive inhibition'). Input words activate lexical frames (i.e. elementary trees anchored to input words) in the mental lexicon, and a network of candidate 'unification links' is set up between frame nodes. These links represent tentative attachments that are graded rather than all-or-none. Candidate links that, due to grammatical or 'treehood' constraints, are incompatible, compete for inclusion in the final syntactic tree by sending each other inhibitory signals that reduce the competitor's attachment strength. The outcome of these local and simultaneous competitions is controlled by dynamic parameters, in particular by the Entry Activation and the Activation Decay rate of syntactic nodes, and by the Strength and Strength Build-up rate of Unification links. In case of a successful parse, a single syntactic tree is returned that covers the whole input string and consists of lexical frames connected by winning Unification links. Simulations are reported of a significant range of psycholinguistic parsing phenomena in both normal and aphasic speakers of English: (i) various effects of linguistic complexity (single versus double, center versus right-hand self-embeddings of relative clauses; the difference between relative clauses with subject and object extraction; the contrast between a complement clause embedded within a relative clause versus a relative clause embedded within a complement clause); (ii) effects of local and global ambiguity, and of word-class and syntactic ambiguity (including recency and length effects); (iii) certain difficulty-of-reanalysis effects (contrasts between local ambiguities that are easy to resolve versus ones that lead to serious garden-path effects); (iv) effects of agrammatism on parsing performance, in particular the performance of various groups of aphasic patients on several sentence types.

Humans↗

PubMed1995

Determination of 5' and 3' DNA triplex interference boundaries reveals the core DNA binding sequence for topoisomerase II.

Previous studies have shown that formation of intermolecular DNA triplexes at sequences that overlap protein binding sites inhibits DNA binding by these proteins. We show that DNA cleavage by eukaryotic topoisomerase II is blocked by triplex formation at sites overlapping and adjacent to the triple binding site. To map precisely the boundaries of triplex interference, we constructed a vector containing enzyme binding sites of different lengths and flanked both 5' and 3' by DNA triplexes. We call this method Triplex Interference Mapping by Binding Element Replacement (TIMBER). Triplex regions within 3 bases 5' or 7 bases 3' of cleavage sites blocked DNA cleavage; triplex formation outside of this region had no effect upon cleavage activity. We conclude that topoisomerase II binding requires unhindered access to the major groove of a duplex DNA binding site in this 10-base region. In addition, the inclusion of topoisomerase II inhibitors yielded the same results for the triplex interference assays despite alterations in DNA cleavage site selection. The statistical analyses of over 500 topoisomerase II cleavage sites (in the presence or absence of inhibitors) suggest a model consistent with the region spanning -3 to +7 (relative to the cleavage site) containing most of the base-specific contacts for topoisomerase II. This triplex interference assay may prove valuable in the characterization of DNA binding sites for other proteins as well, particularly in conjunction with deletion analysis.

Animals↗

PubMed1981

Oxalate secretion in the rat proximal tubule.

Simultaneous capillary and luminal microperfusion studies in the proximal convoluted tubule of the rat were performed to examine the transepithelial secretory flux of [14C]oxalate. Increases in the concentration of oxalate in the capillary solution from 0.096 to 4.3 mM resulted in progressively higher rates of oxalate secretion into the lumen. Further increases in the capillary concentration of oxalate indicated a tendency toward a plateau. The inclusion of para-chloromercuribenzoate, sodium cyanide, indanyloxyacetic acid, furosemide, or para-aminohippurate in the capillary solution significantly lowered the secretory flux of oxalate. the addition of probenecid in a concentration of 10(-4) M inhibited oxalate secretion when the oxalate concentration in the capillary solution ranged between 1.1 and 4.3 mM, but did not affect oxalate secretion at higher capillary concentrations of oxalate. These results indicate that oxalate secretion in the rat proximal tubule is an active carrier-mediated process. When considered in conjunction with prior studies, the present investigations suggest the possibility that more than one oxalate secretory system exists in the rat proximal tubule.

Animals↗

PubMed1992

A physician's guide to smoking cessation.

Claims of the effectiveness of smoking cessation services and products are often misleading. It is important that physicians be well informed in order to make appropriate recommendations to their patients who smoke. In this article smoking cessation products and programs are critically evaluated and issues such as cure rates and validation of self-reported abstinence are discussed. Many commercial products are available to aid in cessation, although none has been proven effective. With the exception of nicotine polacrilex gum and transdermal patches in conjunction with a multicomponent clinic, medications are generally ineffective. Smoking cessation programs range from the provision of self-help materials to multisession groups and clinics. Multicomponent, behavioral-based group programs have been the most successful. Physicians should raise the issue of smoking cessation as frequently as possible with smokers and should recommend the use of smoking cessation products and services as appropriate. Referrals should be made to programs that base their success rates on scientifically accepted standards, including a 1-year follow-up, inclusion of dropouts and nonrespondents in calculating outcome, and biochemical validation of self-reported abstinence. Reports of success rates of 80% to 95% at the end of a 1-year program should be viewed with skepticism. Ideally, whether working independently or through referral, the physician should actively promote smoking cessation for all patients who smoke.

Health Promotion↗

PubMed2000

Role of the cytoplasmic tail of pseudorabies virus glycoprotein E in virion formation.

Glycoproteins M (gM), E (gE), and I (gI) of pseudorabies virus (PrV) are required for efficient formation of mature virions. The simultaneous absence of gM and the gE/gI complex results in severe deficiencies in virion morphogenesis and cell-to-cell spread, leading to drastically decreased virus titers and a small-plaque phenotype (A. Brack, J. Dijkstra, H. Granzow, B. G. Klupp, and T. C. Mettenleiter, J. Virol. 73:5364-5372, 1999). Serial passaging in noncomplementing cells of a virus mutant unable to express gM, gE, and gI resulted in a reversion of the small-plaque phenotype and restoration of infectious virus formation to the level of a gM(-) mutant. Genetic analyses showed that reversion of the phenotype was accompanied by a genomic rearrangement which led to the fusion of a portion of the gE gene encoding the cytoplasmic domain to the 3' end of the glycoprotein D gene, resulting in expression of a chimeric gD-gE protein. Since this indicated that the intracytoplasmic domain of gE was responsible for the observed phenotypic alterations, the UL10 (gM) gene was deleted in a PrV mutant, PrV-107, which specifically lacked the cytoplasmic tail of gE. Regarding one-step growth, plaque size, and virion formation as observed under the electron microscope, the mutant lacking gM and the gE cytoplasmic tail proved to be very similar to the gE/I/M triple mutant. Thus, our data indicate that it is the cytoplasmic tail of gE which is responsible for the observed phenotypic effects in conjunction with deletion of gM. We hypothesize that the cytoplasmic domain of gE specifically interacts with components of the capsid and/or tegument, leading to efficient secondary envelopment of intracytoplasmic capsids.

Animals↗

PubMed1996

Differential interaction with endocytic and exocytic pathways distinguish parasitophorous vacuoles of Coxiella burnetii and Chlamydia trachomatis.

Coxiella burnetii and Chlamydia trachomatis are bacterial obligate intracellular parasites that occupy distinct vacuolar niches within eucaryotic host cells. We have employed immunofluorescence, cytochemistry, fluorescent vital stains, and fluid-phase markers in conjunction with electron, confocal, and conventional microscopy to characterize the vacuolar environments of these pathogens. The acidic nature of the C. burnetii-containing vacuole was confirmed by its acquisition of the acidotropic base acridine orange (AO). The presence of the vacuolar-type (H+) ATPase (V-ATPase) within the Coxiella vacuolar membrane was demonstrated by indirect immunofluorescence, and growth of C. burnetii was inhibited by bafilomycin A1 (Baf A), a specific inhibitor of the V-ATPase. In contrast, AO did not accumulate in C. trachomatis inclusions nor was the V-ATPase found in the inclusion membrane. Moreover, chlamydial growth was not inhibited by Baf A or the lysosomotropic amines methylamine, ammonium chloride, and chloroquine. Vacuoles harboring C. burnetii incorporated the fluorescent fluid- phase markers, fluorescein isothiocyanate-dextran (FITC-dex) and Lucifer yellow (LY), indicating trafficking between that vacuole and the endocytic pathway. Neither FITC-dex nor LY was sequestered by chlamydial inclusions. The late endosomal-prelysosomal marker cation-independent mannose 6-phosphate receptor was not detectable in the vacuolar membranes encompassing either parasite. However, the lysosomal enzymes acid phosphatase and cathepsin D and the lysosomal glycoproteins LAMP-1 and LAMP-2 localized to the C. burnetii vacuole but not the chlamydial vacuole. Interaction of C. trachomatis inclusions with the Golgi-derived vesicles was demonstrated by the transport of sphingomyelin, endogenously synthesized from C6-NBD-ceramide, to the chlamydial inclusion and incorporation into the bacterial cell wall. Similar trafficking of C-NBD-ceramide was not evident in C. burnetii-infected cells. Collectively, the data indicate that C. trachomatis replicates within a nonacidified vacuole that is disconnected from endosome-lysosome trafficking but may receive lipid from exocytic vesicles derived from the trans-Golgi network. These observations are in sharp contrast to those for C. burnetii, which by all criteria resides in a typical phagolysosome.

Animals↗

PubMed1991

Advantages of adoptive chemoimmunotherapy with polyethylene glycol-cultured, antigen-activated, tumor-infiltrated spleen cells for the complete eradication of lethal MOPC-315 plasmacytomas.

The incorporation of polyethylene glycol-6000 (PEG) into the culture media of tumor-infiltrated spleen cells (TISpC) and MOPC-315 stimulator tumor cells at a responder to stimulator cell ratio of 30/1 had been shown to lead to the appearance of CD8+ T-cells that were effective in adoptive chemoimmunotherapy (ACIT) of mice bearing a barely palpable MOPC-315 tumor (J. A. Wise, M. B. Mokyr, and S. Dray, Cancer Res., 49:3613-3619, 1989). Here we show that in the presence of substantially fewer added stimulator tumor cells (responder to stimulator cell ratio, 100/1), the inclusion of PEG in the cultures of TISpC also enhanced the appearance of cells that were highly effective in curing such mice by ACIT. Moreover, these PEG-cultured TISpC were more effective in ACIT than TISpC cultured in the presence of an optimal concentration of recombinant interleukin-2 (60 IU/ml). The potency of the tumor-eradicating activity of the PEG-cultured TISpC in ACIT was further illustrated by their ability to cause the complete regression of a large (20-22 mm) s.c. MOPC-315 tumor in conjunction with a dose of drug that by itself did not cause tumor regression. PEG-cultured TISpC that were effective against MOPC-315 tumor cells in an antigen-specific manner. In fact, PEG-cultured TISpC were more effective than recombinant interleukin-2-cultured TISpC, not only in ACIT, but also in their ability to lyse MOPC-315 tumor cells in vitro. Thus, a direct specific lytic activity against the tumor by cytotoxic T-lymphocytes is the apparent mechanism through which the complete regression of the large tumor burden is brought about by the PEG-cultured TISpC. Finally, we suggest that the incorporation of PEG to render ineffective lymphoid cells effective in ACIT may offer some advantages compared with the incorporation of recombinant interleukin-2 and may be suitable for protocols to generate human cytotoxic cells for cancer therapy when there are relatively low numbers of available tumor cells.

Animals↗

PubMed1993

Does the system of Papanicolaou test nomenclature affect the rate of referral for colposcopy? A survey of family physicians.

OBJECTIVE: To determine whether a new system of Papanicolaou test nomenclature (the Bethesda system) or other physician variables influence recommendations for colposcopy and biopsy for women with borderline to moderately abnormal Papanicolaou test results. We hypothesized that physician demographic and practice variables, in addition to Papanicolaou test nomenclature, would influence recommendations for colposcopy. DESIGN: A survey was mailed to a random sample of 510 active members of the American Academy of Family Physicians. PARTICIPANTS: Three hundred thirty-five (66%) of the eligible physicians responded, representing all 50 states. Of those in active practice, 78% were in private practice, with a mean age of 44 years and a mean time in practice of 10 years. Ninety-three percent of respondents in active practice performed Papanicolaou tests. MAIN OUTCOME MEASURE: Rates of recommendation for colposcopy and biopsy in response to abnormal Papanicolaou test reports framed by a single clinical scenario. RESULTS: Physicians recommended colposcopy more often when the Bethesda nomenclature system was used to describe the results of the Papanicolaou test. These differences were significant for four specific Papanicolaou smear pairs. Inclusion of recommendations for further evaluation strongly influenced physicians to recommend colposcopy. In multivariable analyses, demographic and practice variables were not associated with recommendations for colposcopy. CONCLUSIONS: The Bethesda system of nomenclature, when compared with a traditional descriptive nomenclature system, influenced family physicians to recommend colposcopy and biopsy more often for abnormal Papanicolaou test results presented in a clinical scenario. Greater utilization of technology and higher medical care costs may result from use of the Bethesda system. Guidelines for evaluation of abnormal Papanicolaou test results are needed for use in conjunction with the Bethesda system guidelines for Papanicolaou test reports.

Adult↗

PubMed2003

Rapid sample-mixing technique for transient NMR and photo-CIDNP spectroscopy: applications to real-time protein folding.

We describe the development and application of a novel rapid sample-mixing technique for real-time NMR (nuclear magnetic resonance) spectroscopy. The apparatus consists of an insert inside a conventional NMR tube coupled to a rapid injection syringe outside the NMR magnet. Efficient and homogeneous mixing of solutions in the NMR tube is achieved with a dead time of tens of milliseconds, without modification of the NMR probe or additional hardware inside the magnet. Provision is made for the inclusion of an optical fiber to allow in situ laser irradiation of samples, for example to generate photo-CIDNP (chemically induced dynamic nuclear polarization). An NMR water suppression method has been implemented to allow experiments in H(2)O as well as in deuterated solvents. The performance of the device has been tested and optimized by a variety of methods, including sensitive detection of residual pH gradients and the use of NMR imaging to monitor the extent of mixing in real time. The potential utility of this device, in conjunction with the sensitivity and selectivity of photo-CIDNP, is demonstrated by experiments on the protein hen lysozyme. These measurements involve the direct detection of spectra during real-time refolding, and the use of CIDNP pulse labeling to study a partially unfolded state of the protein under equilibrium conditions. Magnetization transfer from this disordered state to the well-characterized native state provides evidence for the remarkable persistence of nativelike elements of structure under conditions in which the protein is partially denatured and aggregation prone.

Animals↗

PubMed1987

Impact of cattle on the prevalence and severity of trachoma.

Ethiopia is the African country with the largest number of cattle (26 million). Because of the potential impact of cattle on the transmission and severity of trachoma, the major cause of blindness in the country, an attempt is made to document this association to justify the inclusion of the control of cattle pollution in the prevention of blindness. The prevalence of trachoma is lower in pastoralists who herd mainly camels than in pastoralists who herd mainly cattle. In the first group the prevalences of moderate and severe trachoma in children under 10 are 0.9% and trichiasis/entropion in the total population 0.2%, whereas in the second group the prevalences are 45.1% and 4.0% respectively. In Borana pastoralists with and without cattle the prevalence ratio for moderate and severe trachoma is 1.0, whereas the prevalence ratios for severe trachoma and conjunctivitis were higher in the group with cattle, 2.5 and 3.0 (p less than 0.001 for both). The elimination of cattle pollution should reduce the prevalence of severe trachoma by 45.4%. This is the first study presenting evidence of an association between cattle and trachoma. On the basis of this study a strong recommendation is made to the Ministry of Health to control cattle pollution in rural areas as a major strategy to prevent blindness in Ethiopia.

Animal Husbandry↗

PubMed1997

Empirical analyses of BOLD fMRI statistics. I. Spatially unsmoothed data collected under null-hypothesis conditions.

Temporal autocorrelation, spatial coherency, and their effects on voxel-wise parametric statistics were examined in BOLD fMRI null-hypothesis, or "noise," datasets. Seventeen normal, young subjects were scanned using BOLD fMRI while not performing any time-locked experimental behavior. Temporal autocorrelation in these datasets was described well by a 1/frequency relationship. Voxel-wise statistical analysis of these noise datasets which assumed independence (i.e., ignored temporal autocorrelation) rejected the null hypothesis at a higher rate than specified by the nominal alpha. Temporal smoothing in conjunction with the use of a modified general linear model (Worsley and Friston, 1995, NeuroImage 2: 173-182) brought the false-positive rate closer to the nominal alpha. It was also found that the noise fMRI datasets contain spatially coherent time signals. This observed spatial coherence could not be fully explained by a continuously differentiable spatial autocovariance function and was much greater for lower temporal frequencies. Its presence made voxel-wise test statistics in a given noise dataset dependent, and thus shifted their distributions to the right or left of 0. Inclusion of a "global signal" covariate in the general linear model reduced this dependence and consequently stabilized (i.e., reduced the variance of) dataset false-positive rates.

Artifacts↗

PubMed2000

Characterization of metalworking fluid exposure indices for a study of acute respiratory effects.

Although metalworking fluids have been widely used throughout industry for decades, occupational exposures to metalworking fluid aerosols and their constituents have not been well characterized. This article describes an exposure assessment for a study of metalworking fluid aerosols and acute respiratory effects. This exposure assessment was unique in its inclusion of multiple exposure measures relevant to a complex environment, and extensive personal sampling for bacteria and endotoxin. The specific objectives were to: (1) obtain indices of personal exposure to metalworking fluid aerosols in an automotive transmission plant, either directly (by sampling) or indirectly (by estimation), and (2) identify and adjust for sources of error in exposure/dose measures, where possible. No prior studies have characterized personal exposures to metalworking fluid aerosols so extensively. Exposure data were obtained during a pilot phase and three principal rounds of data collection over a 15-month period in conjunction with spirometric testing. Subjects worked in one of two machining departments, Case and Valve Body, or in a comparison department, Final Assembly. The primary exposure measures for this study were thoracic fraction particulate, thoracic fraction bacteria (viable plus non-viable), and total endotoxin. Mean personal air concentrations of thoracic particulate across all study rounds were 0.13 mg/m3 in Final Assembly, 0.32 mg/m3 in Valve Body, and 0.56 mg/m3 in Case. Average personal exposures to thoracic fraction bacteria were 0.38 bacteria/cc in Final Assembly, 0.87 bacteria/cc in Valve Body, and 2.66 bacteria/cc in Case. Average personal endotoxin measurements, collected in Round 3 of the study, were 16.4 endotoxin units (EU)/m3 in Assembly, 34.7 EU/m3 in Valve Body, and 234 EU/m3 in Case. Sump fluid contained on the order of 10(8) bacteria/ml, and 10(4)-10(5) EU/ml. Air concentrations of thoracic particulate, thoracic bacteria, and total endotoxin were highly correlated in metalworking operations. Thus, reducing airborne particulate levels should also reduce ambient bacteria and endotoxin, which are suspect agents of respiratory impairment. The elevated endotoxin levels in Final Assembly were unexpected, and suggest an independent source of endotoxin contamination in this department.

Acute Disease↗

PubMed1994

Electron microscopic findings in hepatic allograft rejection.

Orthotopic liver transplantation is today an accepted surgical procedure for patients with irreversible, end-stage liver disease. Between 1988 and 1993, seven patients (one patient twice) received liver grafts for end-stage liver disease at Howard University Hospital, Washington, DC. In conjunction with the transplant procedure, a total of 32 liver needle biopsy specimens were submitted to the pathology department. Almost half of all liver graft failures are attributed to acute, or in a lesser degree, to chronic rejection. The purpose of this study was to describe the ultrastructural findings in acute cellular rejection and to correlate the ultrastructure with the histology. The key ultrastructural features of acute cellular rejection were: a mixed cellular inflammatory infiltrate in the portal tract, bile duct damage by immunocytes with reduplication of the epithelial basement membrane, endotheliitis, and intramitochondrial crystalline inclusions. It was concluded that electron microscopic investigation significantly contributes to better understanding the immunopathologic mechanism underlying liver allograft rejection.

Graft Rejection↗

PubMed1990

Quantitative, waking EEG research on depression.

Research published in the past decade that used quantitative indices to evaluate the waking EEG characteristics of depressed patients is reviewed. Methodological problems that make results of different research laboratories difficult to compare include diagnostic heterogeneity of depressed groups, lack of inclusion of control subjects, and differences in the EEG techniques. Despite interpretive problems that arise from such substantial variation, consistencies nevertheless emerge. Unmedicated, actively depressed patients appear to exhibit elevated EEG alpha and beta compared to control subjects. Delta and theta distinguished depressed patients from controls in some single studies, but variation in age, specific diagnostic depression categories, and EEG acquisition and analysis techniques rendered these results less definitive. Quantitative EEG differences that may distinguish depressed subject samples from those with other psychiatric disorders are considered. Factors that limit comparability of the findings are discussed in conjunction with strategies that deserve systematic study in future research.

Cerebral Cortex↗