High performance imaging streak camera for the National Ignition Facility.

An x-ray streak camera platform has been characterized and implemented for use at the National Ignition Facility. The camera has been modified to meet the experiment requirements of the National Ignition Campaign and to perform reliably in conditions that produce high electromagnetic interference. A train of temporal ultra-violet timing markers has been added to the diagnostic in order to calibrate the temporal axis of the instrument and the detector efficiency of the streak camera was improved by using a CsI photocathode. The performance of the streak camera has been characterized and is summarized in this paper. The detector efficiency and cathode measurements are also presented.

Infected tracheal diverticulum mimicking an aggressive mediastinal lesion on FDG PET/CT: an interesting case with review of the literature.

The differential diagnosis for intense hypermetabolic mediastinal lesions on positron emission tomography (PET) could benefit from the combined morphological and metabolic information present in a fluorodeoxyglucose (FDG) PET/CT study. We report a case of an infected tracheal diverticulum mimicking an FDG-avid malignancy in a patient with a history of chronic lymphoproliferative disease. We review the literature for a systematic approach in the differential diagnosis of cystic mediastinal lesions. The embryological development of the normal tracheobronchial tree is reviewed, followed by a presentation of various congenital and acquired mediastinal lesions. The characteristic CT findings are described for each lesion and the avidity for FDG on PET is mentioned when references are available. This case emphasises that complicated benign processes should be considered in the differential diagnosis of an FDG-avid mediastinal lesion, even in subgroups of patients with significant risk factors for malignancy.

Initial McGill experience with fluorodeoxyglucose pet/ct staging of soft-tissue sarcoma.

BACKGROUND: Soft-tissue sarcoma spreads predominantly to the lung. The frequency with which positron-emission tomography (pet) detects metastases not already obvious by chest computed tomography (ct) or clinical examination is currently unclear. METHODS: We retrospectively identified cases of soft-tissue sarcoma. Ewing sarcoma, rhabdomyosarcoma, and gastrointestinal stromal tumour were excluded, as were cases in which patients underwent imaging for follow-up, response assessment, or recurrence. Patients all had undergone diagnostic chest ct as part of their staging. Directed studies were requested to follow up on abnormal findings in the clinical history or physical examination. All charts and pre-treatment imaging were reviewed retrospectively. RESULTS: From 2004 to 2008, 75 patients met the criteria for the present review. Their median age was 51 years. In 21% of cases, the primary tumour had been removed (by excisional biopsy or unplanned excision) before staging. Of the previously unresected primary tumours, 97% were avid for fluorodeoxyglucose. Of all tumours, 81% were intermediate or high grade (Fédération Nationale des Centres de Lutte Contre le Cancer grades 2-3). The primary tumour was stage T2b in 69% of cases. The most common primary site was a lower extremity (55%). The most common pathologic diagnoses were leiomyosarcoma (21%), liposarcoma (19%), and synovial sarcoma (17%). At the end of staging, 17% of patients were considered to have metastatic disease. Imaging by pet was negative for distant disease in 64 of the 75 cases. In 7 of the 64 cases, metastatic disease was evident on chest ct (negative predictive value: 88%). Imaging by pet was positive in 8 cases, with 5 of those already known to have metastases, 2 having pathologically proven false positives, and 1 being a new finding of a pulmonary metastasis (positive predictive value: 75%). The pet imaging was indeterminate in 3 patients (none of whom subsequently developed metastatic disease). Two incidental benign parotid tumours were found. Overall, only 1 patient was upstaged as a result of pet imaging (1.3%). In addition, pet did not alter the management of patients already know to have M1 disease (no new organ sites identified). CONCLUSIONS: Although pet may be helpful in specific circumstances, routine use of fluorodeoxyglucose pet imaging for detection of metastatic disease as part of the initial staging of soft-tissue sarcoma added little to imaging by chest ct and was unlikely to alter management in our series.

Dynamics of water-soluble carbon substances and microbial populations during the composting of de-inking paper sludge.

Composting is an alternative method to dispose of de-inking paper sludge (DPS). Today, few studies have investigated the water-soluble carbon (WSC) substances as indicators of the decomposition process and the microbial changes taking place during the composting of DPS. Accordingly, the goal is to study their dynamics during the composting of DPS at three nitrogen levels, 0.6%, 0.7% or 0.9% total N, using mechanical turning. The changes in WSC substances, microbial biomass carbon (MBC) and, total and DPS microbial populations were monitored during 24 weeks. Also, microorganisms were identified and tested for the production of selected enzymes. Regardless of N treatments, the dynamic of WSC substances indicated that cellulose and hemicellulose fractions of DPS fibers were mainly biodegraded during the first 8 weeks while the more resistant carbon (C) fractions were biodegraded thereafter. MBC also evolved regardless of N treatments but was correlated to WSC substances. Its high values decline mostly after 12 weeks indicating the exhaustion of this source of C energy for microbial growth and the stabilisation of DPS organic matter. The dynamic and identified microorganisms were comparable to those observed in other composting processes. However, the results pointed out that those mostly implicated in the hydrolysis of DPS fibers were the thermophilic actinomycetes and fungi and, by comparison to the 0.6% or 0.7% N treatment, they decreased in presence of the 0.9% N treatment. Most microorganisms were hemicellulolytic bacteria, while actinomycetes and fungi were capable of degrading a wide variety of substrates. Overall, dynamics of WSC substances and microbial populations indicated that during composting, DPS decomposition obey a two phase decay while, contrary to the lowest N treatment, the 0.9% N treatment has slowed down this process by harming the important microbial populations implicated in the degradation of DPS fibers.

Estimation of the misclassification rate of self-reported visual disability.

PURPOSE: To estimate the misclassification rate of self-reported visual disabilities in a hospital-based population with known visual impairment. METHODS: Subjects (N=570) were recruited among patients aged 50 years and more and classified to three categories of visual impairment level. The questionnaire was administered to consenting patients through a telephone interview. Data collected from questionnaires and medical records were compared regarding severity of visual impairment. Sensitivity and specificity were determined for each question. Predictive ability and misclassification rates were computed for various prevalences. RESULTS: Questions related to near and far distance visual acuity with glasses have both a good sensitivity (82.6% and 81.8%) and a good specificity (85.6% and 88.9%) for the presence of severe visual impairment. CONCLUSION: The findings allow the determination of the misclassification rate and predictive ability. This could be useful to estimate the prevalence of visual impairment from health surveys.

Composting of de-inking paper sludge with poultry manure at three nitrogen levels using mechanical turning: behavior of physico-chemical parameters.

De-inking paper sludge (DPS) is rich in carbon (C) but poor in nitrogen (N). Thus, it has a high C:N ratio which limits the composting process. Accordingly, the goal of this study was to investigate the effect of three N treatments on DPS composting. Compost piles of 100 m3 were formed by mixing raw DPS with poultry manure and chicken broiler floor litter, giving on average 0.6%, 0.7% and 0.9% total N. The changes in physico-chemical parameters, total weight and fiber losses, and maturity of composting piles of DPS were monitored during 24 weeks. The compost piles had a neutral to alkaline pH throughout the study. Inorganic N decreased whereas organic N increased over time for all treatments. These changes in magnitude were different among N treatments resulting in a final total N content of 0.9% for the 0.6% N treatment whereas final total N contents of 0.7% and 0.9% N were measured for the 0.7% and 0.9% N treatments. The total weight, cellulose and hemicellulose losses were higher in 0.6% N treatment giving the lowest C:N ratio after 24 weeks of composting. However, none of the 24 week-old composts of DPS were mature based on their final C:N ratio and colorimetric test of maturity. Except for copper, their final total trace element contents meet most known standards or guidelines for organic soil conditioners. Overall, 0.6% N treatment was the best to enhance DPS composting using mechanical turning, but a period of more than 24 weeks was required to reach compost maturity.

Synthesis of a broad array of highly functionalized, enantiomerically pure cyclohexanecarboxylic acid derivatives by microbial dihydroxylation of benzoic acid and subsequent oxidative and rearrangement reactions.

[reaction: see text]. We have found that the 1,2-dihydroxylation of benzoic acid with Alcaligenes eutrophus strain B9, first reported in 1971 by Reiner and Hegeman, is readily adapted for the preparation of tens to hundreds of grams of (1S,2R)-1,2-dihydroxycyclohexa-3,5-diene-1-carboxylic acid of >95% ee. This unique substrate undergoes many specific oxidative and rearrangement processes. Among these are transformations of unanticipated chemical novelty and many products that have not been previously described.

Contrast and glare testing in the assessment of visual performance of candidate eyes for penetrating keratoplasty.

PURPOSE: To determine whether visual acuity (VA) measurements performed at low levels of contrast and glare are a better diagnostic tool for determining whether corneal clouding warrants surgery. METHODS: Fifty-nine subjects were recruited from among the candidates for corneal graft. Monocular VA was measured with three Regan contrast VA charts: 96, 25, and 11%, with and without glare provided by the Brightness Acuity Tester (BAT). The discriminative ability of the tests was estimated using the area (AR) under receiver operating characteristic (ROC) curves. Associations between the different VA tests and the Visual Function Index (VF-14) score were studied, using Spearman coefficients. RESULTS: When comparing candidate eyes with contralateral eyes with corneal disease, lower contrasts VA tests provided greater discriminative power. VA measurements made with glare also tended to provide greater discrimination. In fact, discrimination was best with 11% contrast VA with glare, but "testability" was poor. The most practical test in a clinical setting, which retained high discriminative ability (0.798), was the 25% contrast VA with glare. The eye with the best VA correlated strongly with the VF-14, especially at 25% contrast without glare, resulting in an Rs of -0.729. CONCLUSION: Twenty-five percent contrast VA with BAT could help the practitioner to decide whether a corneal transplant is warranted when symptoms of reduced vision are more important than what high-contrast VA might indicate.

Dorzolamide and corneal recovery from edema in patients with glaucoma or ocular hypertension.

PURPOSE: To investigate whether dorzolamide alters corneal hydration control in patients with glaucoma or ocular hypertension. METHODS: Pachymetry, tonometry, and endothelial cell density were measured by a masked observer in 19 subjects with bilateral glaucoma or ocular hypertension. They were treated with 2% dorzolamide in one eye, and with saline in the other, before wearing contact lenses under patched eyes. Corneal thickness, measured each 30 minutes up to 4.5 hours after contact lens removal, enabled estimation of percentage recovery per hour and time for 95% of corneal thickness recovery for both eyes. Seven patients repeated this test after 1 year of dorzolamide use, and their results were compared with those of the preceding year. RESULTS: After induction of hypoxic corneal edema, there was no significant difference between paired corneas in swelling levels (60.0+/-11.8 and 59.8+/-12.9 microm) (P = .94), time to 95% recovery (440.6+/-255.8 and 445.4+/-186.7 minutes) (P = .93), and percentage recovery per hour (38.1%+/-10.9% and 36.1%+/-9.6%) (P = .40). Subjects followed up after 1 year of dorzolamide use did not differ significantly in values of endothelial cell density, percentage recovery per hour, or time to 95% recovery from those obtained a year before. One subject developed persistent corneal edema after his stress test in the eye treated with dorzolamide. CONCLUSION: There is no significant difference in the recovery from induced corneal edema after either a short-term or 1-year use of dorzolamide in patients with glaucoma or ocular hypertension with a normal corneal endothelium. One patient had persistent corneal edema after the stress test was performed on the dorzolamide-treated eye.

The VF-14 index of functional visual impairment in candidates for a corneal graft.

PURPOSE: To validate the Visual Function-14 (VF-14) index of functional visual impairment in candidates for a corneal graft. METHODS: One hundred thirty-four patients who were candidates for a corneal graft participated in this study between August 1996 and February 1997. Demographic, ocular history, best-corrected visual acuity, and detailed ocular examination data were collected. Functional visual impairment information was obtained by telephone interviews using the following: VF-14, SF-36 (Short Form-36, a more generic measure of general health function), and Visual Symptom Score, and four questions measuring the overall amount of trouble with vision, dissatisfaction with vision, ocular pain, and discomfort. RESULTS: The average age of corneal graft candidates was 64 +/- 18 years (range, 18 to 90 years) and 60% were women. The most frequent corneal disease was pseudophakic bullous keratopathy (41%). Ocular comorbidities included glaucoma or ocular hypertension (30%) and cataract (19%). The mean best-corrected visual acuity of the eye scheduled for surgery was 1.33 +/- 0.56 logMAR whereas the best eye best-corrected visual acuity was 0.36 +/- 0.44 logMAR. The mean VF-14 score was 73% +/- 26%, and the internal consistency was high, with a Cronbach alpha value of 0.94. The VF-14 correlated strongly with the best eye best-corrected visual acuity. It also correlated strongly with the Visual Symptom Score, the global measures of trouble and dissatisfaction with vision. Candidates for a corneal graft had low scores for all eight general health concepts evaluated with the SF-36, and the VF-14 correlated with seven of the eight SF-36 subscales. CONCLUSION: The VF-14 is a valid measure of functional visual impairment in candidates for a corneal graft. The Visual Symptom Score and the SF-36 are also useful indices in such patients.

Selective uptake of cholesteryl esters from various classes of lipoproteins by HepG2 cells.

Selective uptake of cholesteryl esters (CE) from lipoproteins by cells has been extensively studied with high density lipoproteins (HDL). It is only recently that such a mechanism has been attributed to intermediate and low density lipoproteins (IDL and LDL). Here, we compare the association of proteins and CE from very low density lipoproteins (VLDL), IDL, LDL and HDL3 to HepG2 cells. These lipoproteins were either labelled in proteins with 125I or in CE with 3H-cholesteryl oleate. We show that, at any lipoprotein concentration, protein association to the cells is significantly smaller for IDL, LDL, and HDL3 than CE association, but not for VLDL. At a concentration of 20 microg lipoprotein/mL, these associations reveal CE-selective uptake in the order of 2-, 4-, and 11-fold for IDL, LDL, and HDL3, respectively. These studies reveal that LDL and HDL3 are good selective donors of CE to HepG2 cells, while IDL is a poor donor and VLDL is not a donor. A significant inverse correlation (r2 = 0.973) was found between the total lipid/protein ratios of the four classes of lipoproteins and the extent of CE-selective uptake by HepG2 cells. The fate of 3H-CE of the two best CE donors (LDL and HDL3) was followed in HepG2 cells after 3 h of incubation. Cells were shown to hydrolyze approximately 25% of the 3H-CE of both lipoproteins. However, when the cells were treated with 100 microM of chloroquine, a lysosomotropic agent, 85 and 40% of 3H-CE hydrolysis was lost for LDL and HDL3, respectively. The fate of LDL and HDL3-CE in HepG2 cells deficient in LDL-receptor was found to be the same, indicating that the portion of CE hydrolysis sensitive to chloroquine is not significantly linked to LDL-receptor activity. Thus, in HepG2 cells, the magnitude of CE-selective uptake is inversely correlated with the total lipid/protein ratios of the lipoproteins and CE-selective uptake from the two best CE donors (LDL and HDL3) appears to follow different pathways.

Presence of CLA-1 and HDL binding sites on syncytiotrophoblast brush border and basal plasma membranes of human placenta.

It is now known that rapid placental and fetal development is associated with elevated levels of circulating high density lipoprotein (HDL) in pregnant women. The main structure implicated in the maternal-fetal exchange is the syncytiotrophoblast, composed of a brush border membrane (BBM), facing the mother, and a basal plasma membrane (BPM), facing the fetus. In order to understand the mechanisms controlling the placental and fetal supplies of cholesterol, we purified both BBM and BPM and verified the presence of HDL binding sites in these membranes. Binding studies using(125)I-HDL(3)show a single affinity binding site on BPM which has a dissociation constant (K(d)) of 3.45+/-0.43 microg protein/ml and a maximal binding capacity (B(max)) of 5.46+/-1.69 microg protein/mg membrane proteins. In BBM, we observed two affinity binding sites, one with a K(d)of 0.62+/-0.03 microg protein/ml and another one with a K(d)of 6.57+/-0.87 microg protein/ml. Their B(max)values were 0.54+/-0.11 and 2.34+/-0.39 microg of HDL(3)/mg membrane proteins, respectively. CLA-1, a putative HDL-receptor of 85 kDa, was detected on both BPM and BBM, together with two apo A-l binding sites of 110 and 96 kDa on BPM and BBM, respectively. These results provide further evidence that human placenta possesses specific sites for HDL binding, underlining the important role of maternal HDL in the transfer of cholesterol from the maternal circulation to the placenta and the fetus.

Selective uptake of cholesteryl ester from low density lipoprotein is involved in HepG2 cell cholesterol homeostasis.

Low density lipoprotein (LDL) can follow either a holoparticle uptake pathway, initiated by the LDL receptor (LDLr), and be completely degraded, or it can deliver its cholesteryl esters (CE) selectively to HepG2 cells. Although high density lipoprotein-CE selective uptake has been shown to be linked to cell cholesterol homeostasis in nonhepatic cells, there is no available information on the effect of LDL-CE selective uptake on hepatic cell cholesterol homeostasis. In order to define the role of the LDL-CE selective uptake pathway in hepatic cell cholesterol homeostasis, we used a cellular model that expresses constitutively a LDLr antisense mRNA and that shows LDLr activity at 31% the normal level (HepG2-all cells). The addition of a specific antibody anti-LDLr (IgG-C7) reduces LDL protein degradation (LDLr activity) to 7%. This cellular model therefore reflects, above all, LDL-CE selective uptake activity when incubated with LDL. The inactivation of LDLr reduces LDL-protein association by 78% and LDL-CE association by only 43%. The LDL-CE selective uptake was not reduced by the inactivation of LDLr. The activities of the various enzymes involved in cell cholesterol homeostasis were measured in normal and LDLr-deficient cells during incubation in the absence or presence of LDL as a cholesterol source. Essentially, 3-hydroxy-3-methylglutaryl coenzyme A reductase and acyl coenzyme A:cholesterol acyltransferase (ACAT) activities responded to LDL in LDLr-deficient cells as well as in normal HepG2 cells. Inhibition of lysosomal hydrolysis with chloroquine abolished the effect measured on ACAT activity in the presence of LDL, suggesting that CE of LDL, but not free cholesterol, maintains cell cholesterol homeostasis. Thus, in HepG2 cells, when LDLr function is virtually abolished, LDL-CE selective uptake is coupled to cell cholesterol homeostasis.

Corneal endothelial cell density in glaucoma.

PURPOSE: We studied corneal endothelial cell density in patients with glaucoma. METHODS: One hundred two patients with glaucoma were compared with 52 patients without glaucoma of the same age group. Exclusion criteria included history of either corneal disease, ocular inflammation, trauma, or surgery other than peripheral iridectomy. The following data were extracted from the patient files: glaucoma type and duration, laser treatments, glaucoma medications, and documented intraocular pressure (IOP) measurements. Specular microscopies were performed on central corneas, endothelial images were analyzed by computerized planimetry, and cell counts were calculated. RESULTS: Corneal endothelial cell counts were significantly lower in patients with glaucoma (2,154 +/- 419 cells/mm2) than in controls (2,560 +/- 360 cells/mm2; t test, p < 0.0001). In the glaucoma group, cell counts were inversely proportional to the means of IOPs. Patients receiving three or four glaucoma medications had lower cell counts than those receiving one or two medications. Cell counts were significantly lower both in primary angle-closure glaucoma and in primary open-angle glaucoma. CONCLUSION: This study suggests that patients with glaucoma may have lower corneal endothelial cell density than those without glaucoma of the same age group. The proposed mechanisms are direct damage from IOP, congenital alteration of the corneal endothelium in patients with glaucoma, glaucoma medication toxicity, or a combination of these.

Validation of French-language versions of the Visual Functioning Index (VF-14) and the Cataract Symptom Score.

OBJECTIVE: To produce and validate French-language versions of the Visual Functioning Index (VF-14), the Cataract Symptom Score (CSS) and two global measures of trouble and satisfaction with vision. DESIGN: Survey by means of telephone interviews conducted 2 weeks apart. SETTING: Ophthalmology clinic of a teaching hospital in Montreal. SUBJECTS: Subjects were recruited among patients with ocular media opacities, such as cataracts and corneal opacities. Of the 71 subjects recruited, 66 (41 French-speaking and 25 French- and English-speaking) completed the study. OUTCOME MEASURES: Visual acuity, scores on vision-related questionnaires and on the 36-Item Short-Form Health Survey (SF-36), a measure of perceived health status. RESULTS: The integral consistency of the French-language versions of the VF-14 and the CSS was high, with Cronbach alpha values of 0.96 and 0.82 respectively. The fidelity with regard to the English-language version, the test-retest reproducibility and the interrater agreement were high (intraclass correlation coefficients > or = 0.80). The correlation between the visual acuity of the better eye and the mean score on all four vision-related measures was statistically significant (p < or = 0.05). The VF-14 scores were also correlated with the score on five of the eight SF-36 subscales (p < or = 0.05). CONCLUSIONS: Our results show that French-language versions of the VF-14, CSS and global measures of trouble and satisfaction with vision are reliable and valid.

Selective uptake of cholesteryl esters of low-density lipoproteins is mediated by the lipoprotein-binding site in HepG2 cells and is followed by the hydrolysis of cholesteryl esters.

The study described in this paper shows that 125I-labelled low-density lipoproteins (LDL) interact with high- and low-affinity binding sites on human hepatoma (HepG2) cells. The former site is the LDL receptor and the latter is the lipoprotein-binding site (LBS). The association of 125I-labelled LDL and [3H]cholesteryl ethers-LDL with HepG2 cells revealed a 4-fold selective uptake of cholesteryl esters (CE) in a 4 h incubation period, which correlated with the depletion of CE mass in LDL. This selective uptake was not observed when the cells were incubated in the presence of a 100-fold excess of high-density lipoprotein 3, conditions where only the LDL receptor is being monitored. Also, no reduction in uptake was observed in the presence of IgG-C7, an anti-(LDL receptor) monoclonal antibody. Both findings indicate that the selective uptake occurs through the LBS and that the LBS contributes more to the entry of CE from LDL into the cell than does the LDL receptor. The fates of CE entering the cell via the LDL receptor and the LBS were also followed. To achieve this, LDL were labelled with [3H]cholesteryl oleate and the hydrolysis of [3H]cholesteryl oleate was monitored. The results indicated that 45% of the CE were hydrolysed after a 4 h incubation period, irrespective of the site of entry. Chloroquine (100 microM) was shown to inhibit hydrolysis, indicating that lysosomal enzymes were responsible for the hydrolysis of LDL-CE, whichever pathway was used. Thus our results reveal, for the first time, that the mass of CE entering the cell via the LBS is substantial and that hydrolysis of CE is by lysosomal enzyme activity. Overall, this suggests that the LBS has significant physiological importance.

Metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone by hamster respiratory tissues cultured with ellagic acid.

Previous studies have shown that the nicotine-derived N-nitrosamine-4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) induces tracheal papillomas and lung carcinomas in Syrian golden hamsters. In this study, we showed that hamster tracheal and lung explants metabolize NNK by alpha-carbon hydroxylation, pyridine N-oxidation and carbonyl reduction. alpha-Methylene hydroxylation and methyl hydroxylation yield methylating and pyridyloxobutylating intermediates, respectively. Levels of binding of the pyridyloxobutyl moiety to explant proteins was 200 times lower than the total amount of metabolites formed by alpha-carbon hydroxylation and released in the culture medium. Viable and heat-treated lung explants were cultured with [CH3-3H]NNK or [5-3H]NNK. In viable explants, the rate of binding of the methyl group was 2-fold higher than the rate of binding of the pyridyloxobutyl moiety of NNK. Heat treatment reduced 54-fold the binding of [CH3-3H] NNK but only 5-fold the binding [5-3H]NNK. Tracheal explants were cultured with [5-3H]NNK (5.6 microM) and ellagic acid (EA, 10 microM), a naturally-occurring plant phenol. EA did not inhibit any of the three metabolic pathways nor the binding of the pyridyloxobutyl moiety to explant proteins. Lung explants were cultured with NNK (3.7 microM) and with or without EA (100 microM). EA inhibits alpha-carbon hydroxylation by 19% and the overall metabolism of NNK by 6%. Formation of 7-methylguanine and O6-methylguanine was observed in lung explants and the levels of both adducts were reduced by EA (100 microM). These results suggest that high concentrations of EA modulate the metabolism of NNK and that NNK does not necessarily require enzymatic activation to bind to protein.

Production of mutacin-like substances by Streptococcus mutans.

Production of inhibitory substances by strains of the Streptococcus mutans group is well documented, but the nature of the substances implied is often unknown. Of nine laboratory strains known to produce inhibitory substances, the optimal conditions for producing inhibition zones on solid media were found to vary between strains but good production was generally obtained on all-purpose media with Tween 80 at 37 degrees C after 2-4 days of aerobic incubation. Streptococcus sanguis Ny101 was found to be more sensitive than Streptococcus rattus LG-1 to all inhibitory substances produced by the S. mutans strains tested. While all strains showed some inhibition, only six showed inhibition after neutralization; arginine incorporated in agar at 0.75% completely eliminated all inhibition zones. However 1% arginine in the overlays did not affect the production of inhibition zones by strains of S. mutans C67-1, Ny257, Ny266, and T8. These strains were shown to elaborate (in a reproducible fashion) inhibitory substances which were not organic acids. Inhibitory activity was never obtained in liquid preparations, except for strains Ny257 and T8 where it was found to be very unstable.

In vitro and in vivo modulation of the bioactivation of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in hamster lung tissues.

The metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) by hamster lung explants was studied. The three major metabolic pathways were alpha-C-hydroxylation (activation), pyridine N-oxidation (deactivation) and carbonyl reduction. alpha-C-Hydroxylation and pyridine N-oxidation were linear with time (0.5-5 h) and number of explants per dish (3-10). Addition of [2-(diethylamino)ethyl 2,2-diphenylpentenoate] hydrochloride (SKF-525A) to the culture medium reduced alpha-C-hydroxylation and pyridine N-oxidation. alpha-C-Hydroxylation was enhanced by treatment of the hamsters with the two cytochrome P-450 inducers, phenobarbital and 3-methylcholanthrene. These results suggest that cytochrome P-450 monooxygenases are involved in the activation of NNK by alpha-C-hydroxylation. Three groups of hamsters were fed a control diet or diet supplemented with 2% 2(3)-tert-butyl 4-hydroxyanisole (2(3)-BHA) or given a 0.002% solution of (S)-nicotine to drink for two weeks. Lung explants were then cultured with NNK in vitro. Treatment with 2(3)-BHA and (S)-nicotine induced the alpha-C-hydroxylation pathways. Pyridine N-oxidation was increased by (S)-nicotine treatment. These results indicate that dietary factors and tobacco smoke components can modulate the metabolism of NNK.