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S A Meyer

Publications and source records attributed to S A Meyer.

At least 19 recordsLinked to original sources
PubMed1999

Evidence for site-specific bioactivation of alachlor in the olfactory mucosa of the Long-Evans rat.

Alachlor (2-chloro-2',6'-diethyl-N-[methoxymethyl]-acetanilide) is a restricted-use chloracetanilide herbicide which has been shown previously to produce a dose-dependent incidence of olfactory mucosal tumors in rats following chronic dietary exposure. However, the mechanism of alachlor carcinogenicity is poorly understood. Alachlor was administered i.p. to male Long-Evans rats for up to 28 days at doses that are carcinogenic in chronic studies in order to study olfactory lesion development and alterations in cell proliferation. Neither treatment-related olfactory mucosal lesions nor regenerative cell proliferation, as assessed with BrdU labeling, was detected. In vitro genotoxicity studies using Salmonella typhimurium strain TA100 showed that alachlor was non-mutagenic in the absence of metabolic activation. When pre-incubated with an olfactory mucosal S9 activation system, alachlor induced a weak, dose-dependent mutagenic response at 500-1250 micrograms/plate, with toxicity at higher doses. In contrast, an S9 activation system derived from nasal respiratory mucosa, the tissue physically juxtaposed with the olfactory mucosa but reportedly not susceptible to alachlor-induced tumors, did not produce a mutagenic response for alachlor or the positive control. Thus, this result suggested site-specificity of alachlor activation consistent with the target site of carcinogenicity. The mutagenicity of alachlor to Salmonella, in the presence of an olfactory mucosal-activating system, was confirmed by a limited positive response in the mouse lymphoma assay. Here there were increases in small colony mutants (indicative of chromosomal effects) as well as large colony mutants (which reflect gene mutations). This study suggests that target tissue bioactivation of alachlor results in the formation of one or more mutagenic metabolite(s), which may be critical in alachlor-induced nasal tumorigenesis.

Acetamides↗
PubMed1997

Application of sonomicrometry and multidimensional scaling to cardiac catheter tracking.

This paper describes a technique for tracking the three-dimensional (3-D) position of a cardiac catheter using sonomicrometry and the mathematical method of multidimensional scaling (MDS). Sonomicrometry is used to measure the distances between ultrasonic transceivers. MDS is then used to calculate the 3-D coordinates of the ultrasonic transceiver locations, including the catheter tip, from the measured distances. Feasibility of catheter tracking was initially studied using simulated data from a geometric model in which the actual coordinates of all transceivers were known. The method was then shown to be feasible in vivo by tracking a catheter-mounted piezoelectric transducer using seven reference crystals sewn to the epicardial surface of a sheep heart. Simulation results indicate that a catheter can be tracked with a root-mean-square (rms) error of 1.51 +/- 0.05 mm and an average-distance error of e = 1.06 +/- 0.27 mm using 12 reference points. In vivo results showed acceptable stress values (G < 0.05) for 95% of the data samples with an average-distance error of e = 0.52 +/- 0.66 mm. These simulation and experimental results show that sonomicrometry and MDS can be used to accurately localize the 3-D position and track the motion of a catheter tip within the heart.

Cardiac Catheterization↗
PubMed1997

Retropatellar contact stress in simulated patella infera.

Six fresh-frozen cadaver knee joints were used to study changes in retropatellar contact mechanics accompanying patella infera. The knees were tested on a servohydraulic testing machine under conditions simulating stair descent at 10 degrees, 30 degrees, 60 degrees, and 90 degrees of knee flexion. A slotted metallic block mechanism embedded in the region of the tibial tubercle allowed selective distal offset of the patellar tendon insertion so as to model conditions of 0, 6, 13, 19, and 25 mm of patella infera. Patellofemoral and quadriceps tendofemoral contact areas and contact stresses were recorded using Pressensor contact film and quantitated using digital image analysis. Patella infera significantly altered retropatellar contact mechanics. Contact areas migrated proximally on the patella and decreased in size with progressive severity of patella infera. However, the peak and spatial mean retropatellar contact stresses were not elevated correspondingly. Apparently, quadriceps tendofemoral contact was initiated at progressively lower angles of knee flexion as the patella infera progressed. Under conditions of extreme infera at high flexion angles, the magnitude of tendofemoral contact force approached that of retropatellar contact force. These data indicate that in patella infera, patellofemoral contact stresses are not elevated appreciably. Therefore, the disabling symptoms associated with patella infera may be due to factors other than local mechanical overload.

Humans↗
PubMed1996

Simplified PCR-SSO procedure for DQA and DQB typing. Simultaneous hybridization of two probes to one membrane.

To simplify DQA and DQB oligotyping, we applied our improved PCR-SSO procedure for DR typing. We used 12 oligonucleotide probes for DQA typing and 18 for DQB typing. Oligonucleotide probes that require the same hybridization and stringent washing conditions were selected as pairs for simultaneous hybridization to a dot-blot membrane containing various DNA samples. One probe of each pair was labeled with digoxigenin and the other with biotin. After hybridization, the dot-blot membranes were incubated with a mixture of conjugates. Specific binding of the corresponding DNA probes was visualized on an X-ray film using a chemiluminescent substrate (CSPD) and by staining using a chromogenic substrate (TMB). This approach, previously employed for DR typing, is also suitable for DQA and DQB oligotyping and significantly reduces the labor inherent in PCR-SSO typing.

Genotype↗
PubMed1996

Epidermal protein kinase C-beta 2 is highly sensitive to downregulation and is exclusively expressed in Langerhans cells: downregulation is associated with attenuated contact hypersensitivity.

Treatment of mice with multiple topical applications of 12-O-tetradecanoylphorbol-13-acetate (TPA) or diacylglycerol resulted in a preferential decrease in epidermal protein kinase C-beta 2 (PKC-beta 2) compared with PKC-alpha as determined by western analysis. When PKC-alpha was decreased by 40%, PKC-beta 2 could no longer be detected, suggesting that PKC-beta 2 is more sensitive to downregulation, and/or specific epidermal cell types that contain PKC-beta 2 are more sensitive to TPA/diacylglycerol. To address this issue, we isolated Langerhans cells (LCs) from epidermal cell suspensions with immunomagnetic beads and an antibody to the class II major histocompatibility complex. Northern blot analysis revealed a PKC-beta 2 signal in isolated LCs that was 40-fold greater than that observed in unfractionated epidermal cells, and no PKC-beta 2 signal was detected in epidermal cells depleted of LCs, indicating that PKC-beta 2 is expressed exclusively in LCs within the epidermis. Western blot analysis confirmed the presence of PKC-beta 2 in LCs. PKC-beta 2 was highly sensitive to downregulation, because a single application of TPA resulted in a 90% loss of PKC-beta 2 within 6 h without a decrease in the number of LCs. To determine whether the decreased level of PKC-beta 2 within LCs was associated with an alteration in contact hypersensitivity, we treated mice with only a single application of TPA, and 6 hours later mice were sensitized with 2,4-dinitrofluorobenzene on the same dorsal area. Subsequent challenge revealed a 60% decrease in contact hypersensitivity in TPA-treated mice. These data indicate that (i) within the epidermis, PKC-beta 2 is highly sensitive to downregulation and is exclusively expressed in LCs, and (ii) the downregulation of PKC-beta 2 is associated with impaired LC function with respect to contact hypersensitivity.

Animals↗
PubMed1994

A polymerase chain reaction-sequence-specific oligonucleotide procedure for HLA class II typing using biotin- and digoxigenin-labeled probes simultaneously in hybridization.

To simplify PCR-SSO HLA-DRB generic typing, we labeled eight of 15 oligonucleotide probes with DIG and the others with biotin, and hybridized each dot blot with both a biotin-labeled probe and a DIG-labeled probe simultaneously. We chose oligonucleotide pairs which require the same hybridization and stringent washing conditions and do not compete with each other during hybridization. After incubation with a mixture of anti-DIG Fab fragment-alkaline phosphatase and streptavidin-peroxidase conjugates, specific binding of the DIG-labeled probe was revealed by a chemiluminescent substrate (CSPD) and specific binding of the biotin-labeled probe was subsequently visualized by a chromogenic substrate (TMB). The sensitivity of both probes was similar and gave comparable hybridization signals. Using this simplified procedure, the number of hybridizations or dot blots can be reduced to half the usual amount and the labor involved in PCR-SSO typing significantly reduced.

Base Sequence↗
PubMed1994

Synergistic interaction between the non-phorbol ester-type promoter mirex and 12-O-tetradecanoylphorbol-13-acetate in mouse skin tumor promotion.

Mirex, an organochlorine pesticide and non-genotoxic rodent hepatocarcinogen, is also a potent non-phorbol ester-type promoter of mouse skin tumors. Mirex, unlike most other skin tumor promoters, is not a significant epidermal hyperplasiogen even at a maximally promoting dose (200 nmol). Experiments described here examined whether tumor promotion by mirex and 12-O-tetradecanoylphorbol-13-acetate (TPA) are mediated through different mechanisms as indicated by their additivity when co-applied to 7,12-dimethyl-benz[a]anthracene (DMBA, 200 nmol)-initiated female CD-1 mouse skin. Instead of the additive response of 14 plus 5 tumors/mouse predicted from mice promoted for 20 weeks (2x/week) with either mirex (200 nmol) or TPA (2 nmol) respectively, their co-application yielded 35 tumors/mouse. This synergy with TPA was specific to mirex since a structurally related compound, chlordecone (Kepone) was inactive. Mirex plus TPA-promoted papillomas contained a c-Ha-ras A182-->T mutation as frequently (13/14) as those promoted by mirex or TPA alone, suggesting that these DMBA-initiated/co-promoted papillomas were not atypical in this genotypic marker. Promotional synergy with mirex was only observed with a submaximal promoting dose of 2 nmol TPA; 5 or 8 nmol TPA plus mirex gave additive or less tumor multiplicities. This synergistic multiplicity with mirex plus 2 nmol TPA (35 tumors/mouse) approximated the sum of individual responses to 200 nmol mirex (14 tumors/mouse) and the maximally promoting dose of TPA (12 nmol), 24 tumors/mouse, suggesting that mirex potentiated the promotional activity of TPA, as well as promoted through a mirex-specific mechanism. Epidermal DNA synthesis induced by 2 nmol TPA was potentiated by mirex, further supporting a role for mirex in potentiation of epidermal TPA activity. Collectively, these studies suggest that mirex affects two possibly related responses: (i) promotion through a distinct mirex-specific mechanism, and (ii) potentiation of a mechanism mediating the promotional activity of TPA.

Adenine↗
PubMed1994

[HLA-DR typing using PCR-SSO with simultaneous hybridization of each dot blot membrane with a digoxigenin- and a biotin-marked probe].

Here we present a PCR-SSO procedure designed to simplify HLA-DR typing. We labelled 8 of a total of 16 oligonucleotide probes with digoxigenin, the others with biotin, and formed 8 pairs, each containing a digoxigenin- as well as a biotin-labelled probe. Each pair was hybridized simultaneously to one of eight dot blot membranes containing the DNA to be typed. Specific binding was detected by incubation with a mixture of the appropriate conjugates followed by sequential addition first of a chemiluminescent substrate to detect the digoxigenin-labelled probe and then a chromogenic substrate for detection of the biotin-labelled probe. With this procedure, the specific binding of two different probes to the same dot blot membrane could be evaluated, considerably reducing the labor inherent in PCR-SSO typing.

Biotin↗
PubMed1993

Unrelatedness of groups of yeasts within the Candida haemulonii complex.

Isoenzyme and protein profiles of clinical isolates initially identified as Candida haemulonii demonstrated the presence of two distinct groups. DNA relatedness studies with representative cultures confirmed the presence of two species. Physiological features that can be used to separate two groups within C. haemulonii are reported.

Candida↗
PubMed1993

Minimal role of enhanced cell proliferation in skin tumor promotion by mirex: a nonphorbol ester-type promoter.

Mirex, a chlorinated hydrocarbon previously used as a systemic insecticide and flame retardant, is a nongenotoxic hepatocarcinogen in both rats and mice. In liver, mirex induced biochemical responses and hyperplasia characteristic of increased cell proliferation, which is consistent with its role as a liver tumor promoter. We have recently shown that mirex is a potent nonphorbol ester-type skin tumor promoter in 7, 12-dimethylbenz[a]anthracene (DMBA)-initiated mice. However, unlike its effect in liver, a single topical application of mirex to skin does not induce the acute biochemical responses, such as increased epidermal DNA synthesis and ornithine decarboxylase activity, indicative of increased cell proliferation. Multiple topical applications of mirex over a 1 month period induced only a minimal increase in the number of epidermal nucleated cell layers, which contrasts with definitive hyperplasia induced by a comparable tumor-promoting dose of 12-O-tetradecanoylphorbol-13-acetate (TPA). Collectively, these data indicated that mirex is promoting through a novel mechanism. Further evidence that mirex promotes tumors through a mechanism distinct from that of the prototypical skin tumor promoter, TPA, was obtained by examining the effect of their simultaneous co-treatment. The co-application of mirex and TPA yielded a tumor multiplicity greater than the sum of the responses of each promoter individually. In summary, our results demonstrate that mirex, a carcinogenic and hyperplastic agent in liver, is also a very effective tumor promoter in mouse skin, but suggest that mirex operates via a novel mechanism in skin that may involve only a minimal role for enhanced cell proliferation.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1993

Stress fractures of the foot and leg.

Stress fractures are overuse injuries of bone. Basketball players are particularly prone to develop the notoriously "troublesome" stress fractures of the foot and leg. This article reviews the pathogenesis, epidemiology, diagnosis, and treatment of stress fractures, with specific emphasis on the care of the basketball athlete.

Basketball↗
PubMed1992

The chlorinated pesticide mirex is a novel nonphorbol ester-type tumor promoter in mouse skin.

The hepatocarcinogenic organochlorine pesticide, mirex, was examined as a tumor promoter in the mouse skin initiation-promotion model. Female CD-1 mice were initiated with 200 nmol 7,12-dimethylbenz[a] anthracene and topically promoted three times weekly for 20 weeks with doses of 25, 50, 100, or 200 nmol mirex. Mirex promoted tumors at all dose levels in a dose-dependent manner. At 20 weeks, mice promoted with 25, 50, 100, and 200 nmol mirex developed an average of 0.2, 4, 10, and 16 tumors per mouse with a 10, 60, 93, and 96% incidence of tumor-bearing mice, respectively. With continued treatment to 34 weeks, mice promoted with 25, 50, and 100 nmol mirex developed an average of 0.7, 7, and 12 tumors per mouse with a 27, 85, and 100% incidence of tumor-bearing mice, respectively. These results demonstrate that mirex is a very effective tumor promoter in mouse skin. The effect of mirex on several biochemical and morphological events associated with tumor promotion was then investigated. Mirex did not stimulate epidermal protein kinase C activity in vitro. Unlike the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate, a single topical application of mirex (200 nmol) did not increase [3H]thymidine incorporation into epidermal DNA up to 108 h after application. Furthermore, multiple applications of 200 nmol mirex (3 times weekly for 4 weeks) resulted in only a very weak proliferative response; mirex increased the number of nucleated epidermal cell layers from 1 to 2 in acetone-treated controls to 2 to 3 while 2 nmol 12-O-tetradecanoylphorbol-13-acetate produced 6 to 7 nucleated cell layers. Mirex (200 nmol) did not induce ornithine decarboxylase activity up to 56 h after a single topical application. Collectively, these data indicate that mirex is a novel nonphorbol ester-type tumor promoter in mouse skin.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1992

DNA relatedness, karyotyping and gene probing of Candida tropicalis, Candida albicans and its synonyms Candida stellatoidea and Candida claussenii.

Isolates of Candida albicans with varied phenotypes, including sucrose-negative variants (C. stellatoidea, serotypes A and B) and avirulent germ tube-negative forms (C. claussenii) showed significant (greater than 90%) DNA relatedness to classical C. albicans, but insignificant relatedness to C. tropicalis and sucrose-negative C. tropicalis. A transverse alternating-field gel electrophoresis procedure (TAFE) showed discrete karyotype patterns among the phenotypic variants of C. albicans including the sucrose-negative C. stellatoidea. The number of chromosome-sized DNA bands for C. tropicalis (7 bands) were within the range of bands observed for C. albicans (5 to 10 bands). The general DNA-migration pattern for C. albicans appeared distinct from that of C. tropicalis. An aspartyl proteinase (PrA) gene probe from C. albicans hybridized with chromosomal DNA from C. albicans, C. claussenii and C. stellatoidea but not with that from C. tropicalis.

Aspartic Acid Endopeptidases↗
PubMed1992

Intestinal calcium transport and calcium extrusion processes at the basolateral membrane.

The intestinal absorption of calcium has been proposed to occur by the transcellular transfer of Ca2+ through the enterocyte proper and between the cells of the intestinal epithelium, i.e., the paracellular path. Attention in this report is given to the transcellular models of Ca2+ absorption and, more specifically, the Ca2+ extrusion events occurring at the basolateral membrane. These extrusion processes include the operation of an ATP-dependent Ca2+ pump and a Na+/Ca2+ exchanger, as well as exocytosis as the terminal event in a proposed vesicular transport mechanism. Evidence for the presence of an ATP-dependent Ca2+ pump at the basolateral membrane is documented and illustrated with biochemical and immunological data from studies on the avian intestinal basolateral membrane. As shown immunohistochemically, the Ca2+ pump was primarily localized on the enterocyte basolateral membrane. The ATP-dependency and vitamin D enhancement of Ca2+ uptake by isolated basolateral membrane vesicles are shown. Western blot analysis of intestinal mucosa, by using a monoclonal antibody produced against the erythrocyte Ca2+ pump, indicated that the number of pump units is increased by 1,25-dihydroxycholecalciferol. The possible involvement of calbindin-D28K as a direct stimulator of the Ca2+ pump is discussed, and the quantitative relationship between Ca2+ transport rates and Ca2+ pumping activity has been estimated. Information related to the basolateral membrane Na+/Ca2+ exchanger and the vesicular transport model of Ca2+ absorption is also briefly reviewed.

Animals↗
PubMed1991

Reversible and phorbol ester-specific defect of protein kinase C translocation in hepatocytes isolated from phenobarbital-treated rats.

Phorbol ester-induced translocation of the calcium/phospholipid-dependent protein kinase, protein kinase C (PKC), from soluble to particulate cell fractions was inhibited in primary cultures of hepatocytes isolated from rats chronically exposed to the liver tumor promoter phenobarbital (PB). Inhibition of translocation (34%) was significant after a 15-min treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA, 500 nM); an 85% inhibition was observed after 60 min. In contrast, the translocation responses to two non-phorbol ester activators of PKC, ATP (1 mM) and arginine-vasopressin (0.1 microM), were not significantly impaired. Assessment of total PKC specific activity revealed that translocation induced by TPA and the two nonphorbol activators was not associated with PKC degradation in hepatocytes from either control or PB-exposed rats. The defect in TPA-induced translocation was correlated with an impaired down-regulation of the hepatocyte surface receptor for epidermal growth factor in hepatocytes from PB-exposed rats. Chronic exposure to PB did not affect the total content or specific activity of PKC in whole liver, nor did it affect the distribution of PKC activity between soluble and particulate fractions in unstimulated liver or hepatocytes. However, both the diminished epidermal growth factor receptor response and the inhibition of TPA-induced PKC translocation were reversed by withdrawal of PB for 2 to 4 weeks. Hepatocytes isolated from female rats were found to contain a 3- to 4-fold greater PKC specific activity and content than hepatocytes from male rats. However, no sex-related differences were observed in PKC distribution or in the modulation of translocation by chronic PB exposure and withdrawal. Immunoblotting of partially purified liver extracts revealed that the defect in phorbol ester-induced translocation was not caused by altered expression of PKC isozymes. PKC isozymes II and III, but not I, were detected, and their amounts were unaffected by PB exposure, although higher levels were detected in female relative to male livers. These data demonstrate reversible inhibition of phorbol ester-induced PKC activation by the liver tumor promoter, PB, and suggest that PB alters a component of the PKC-signaling pathway other than the expression of PKC isozymes.

Animals↗