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M S Bartlett

Publications and source records attributed to M S Bartlett.

At least 19 recordsLinked to original sources
PubMed2007

Human and computer recognition of facial expressions of emotion.

Neuropsychological and neuroimaging evidence suggests that the human brain contains facial expression recognition detectors specialized for specific discrete emotions. However, some human behavioral data suggest that humans recognize expressions as similar and not discrete entities. This latter observation has been taken to indicate that internal representations of facial expressions may be best characterized as varying along continuous underlying dimensions. To examine the potential compatibility of these two views, the present study compared human and support vector machine (SVM) facial expression recognition performance. Separate SVMs were trained to develop fully automatic optimal recognition of one of six basic emotional expressions in real-time with no explicit training on expression similarity. Performance revealed high recognition accuracy for expression prototypes. Without explicit training of similarity detection, magnitude of activation across each emotion-specific SVM captured human judgments of expression similarity. This evidence suggests that combinations of expert classifiers from separate internal neural representations result in similarity judgments between expressions, supporting the appearance of a continuous underlying dimensionality. Further, these data suggest similarity in expression meaning is supported by superficial similarities in expression appearance.

Artificial Intelligence↗
PubMed2001

Alteration in expression of the rat mitochondrial ATPase 6 gene during Pneumocystis carinii infection.

BACKGROUND: Pneumocystis carinii causes pneumonia in immunocompromised patients with a high morbidity and mortality rate, but the interaction between this organism and the host cell is not well understood. The purpose of this research was to study the response of host cells to P. carinii infection on a molecular level. RESULTS: The technique of mRNA differential display was used to detect genes whose expression may be affected by P. carinii infection. The nucleotide sequence of one differentially displayed DNA fragment was found to be identical to that of the rat mitochondrial ATPase 6 gene, which is a subunit of the F0F1-ATP synthase complex. A four-fold increase in expression of this gene was verified by Northern blot analysis of total RNA extracted from P. carinii-infected rat lung versus that from mock-infected rat lung. Localization of the cells containing ATPase 6 mRNA was accomplished by in situ hybridization. In sections of non-infected rat lung, these cells were found lining the distal parts of the respiratory tree and in apical areas of the alveoli. Histological location of these cells suggested that they were Clara cells and type II pneumocytes. This hypothesis was confirmed by co-localizing the mRNAs for ATPase 6 and surfactant protein B (SP-B) to the same cells by two-color fluorescent in situ hybridization. CONCLUSIONS: The ATPase 6 gene is over expressed during P. carinii infection, and type II pneumocytes and Clara cells are the cell types responsible for this over-expression.

Adenosine Triphosphatases↗
PubMed2001

Activities and conformational fitting of 1,4-naphthoquinone derivatives and other cyclic 1,4-diones tested in vitro against Pneumocystis carinii.

Atovaquone is a chemotherapeutic agent used to treat pneumonia caused by Pneumocystis carinii in some immunocompromised patients. A set of cyclic 1,4-diones were tested in vitro for ability to inhibit growth of P. carinii, including 22 variously substituted 1,4-naphthoquinones, one bis-1,4-naphthoquinone, and three other quinones. For comparison, the antipneumocystic primaquine and its 5-hydroxy-6-desmethyl metabolite were also tested. At 1.0 microg/ml, seven compounds inhibited growth by at least 39%, with atovaquone at 92%; of these seven, five are 2-hydroxy-1,4-naphthoquinones, while one is a 2-chloro- and another is a 2-methyl-1,4-naphthoquinone. At 0.1 microg/ml, however, the most active compound tested was the primaquine metabolite, which inhibited growth by more than 42% at this concentration. To ascertain a structure-activity relationship, all 1,4-naphthoquinones were compared conformationally by means of computer-based molecular modeling (Spartan) incorporating the Sybyl force field. Without exception, for all 21 monomers tested, the substituent at position 3 of the 1,4-naphthoquinone favored activity most strongly when it simultaneously occupied (i) space centered at about 3 A from position 3, without projecting steric bulk from the area encompassed by atovaquone's cyclohexyl ring, and (ii) roughly planar space at about 7.3 A from position 3, without projecting steric bulk perpendicularly. This structure-activity relationship may prove useful in the rational design of better antipneumocystis agents.

Antifungal Agents↗
PubMed2001

Internal transcribed spacer regions of rRNA genes of Pneumocystis carinii from monkeys.

Analysis of sequence variations among isolates of Pneumocystis carinii f. sp. macacae from 14 Indian rhesus monkeys (Macaca mulatta) at the internal transcribed spacer (ITS) regions of the nuclear rRNA gene was undertaken. Like those from P. carinii f. sp. hominis, the ITS sequences from various P. carinii f. sp. macacae isolates were not identical. Two major types of sequences were found. One type of sequence was shared by 13 isolates. These 13 sequences were homologous but not identical. Variations were found at 13 of the 180 positions in the ITS1 region and 28 of the 221 positions in the ITS2 region. These sequence variations were not random but exhibited definite patterns when the sequences were aligned. According to this sequence variation, ITS1 sequences were classified into three types and ITS2 sequences were classified into five types. The remaining specimen had ITS1 and ITS2 sequences substantially different from the others. Although some specimens had the same ITS1 or ITS2 sequence, all 14 samples exhibited a unique whole ITS sequence (ITS1 plus ITS2). The 5.8S rRNA gene sequences were also analyzed, and only two types of sequences that differ by only one base were found. Unlike P. carinii f. sp. hominis infections in humans, none of the monkey lung specimens examined in this study were found to be infected by more than one type of P. carinii f. sp. macacae. These results offer insights into the genetic differences between P. carinii organisms which infect distinct species.

Animals↗
PubMed2000

The orientation of DNA in an archaeal transcription initiation complex.

RNA polymerase from the hyperthermophile archaeon Pyrococcus furiosus (Pfu) forms specific and transcriptionally active complexes with its conjugate transcription factors TBP (the archaeal TATA binding protein homolog) and TFB (the archaeal homolog of eukaryotic RNA polymerase II and III transcription factors TFIIB and Brf) at the Pfu glutamate dehydrogenase promoter. A photochemical crosslinking method was used to map the vicinity of the catalytic subunits of Pfu RNA polymerase to DNA locations distributed along the polymerase-promoter interface. The largest component of this archaeal polymerase is split into two subunits, A' and A", whose relatively sharp boundary of DNA crosslinking (probed on the transcribed strand) is centered five to six base pairs downstream of the transcriptional start site. A strong argument based on this information, on the well-defined homology between the core bacterial, archaeal and eukaryotic RNA polymerase subunits, and on the recently determined structure of a bacterial RNA polymerase specifies the directionality of DNA in the archaeal transcription complex and its trajectory downstream of the transcriptional start site.

Archaeal Proteins↗
PubMed2000

Diagnosis of Pneumocystis carinii pneumonia in human immunodeficiency virus-infected patients with polymerase chain reaction: a blinded comparison to standard methods.

Pneumocystis carinii pneumonia (PCP) is an important cause of morbidity and death among persons with human immunodeficiency virus (HIV) infection. Polymerase chain reaction (PCR) analysis of respiratory specimens has been investigated as a rapid diagnostic method. We have previously reported on the utility of this technique for diagnosing PCP in HIV-infected patients. In this report we evaluate PCR used in a blinded study design to avoid biases inherent to retrospective and nonblinded studies. The diagnosis of PCP was established on the basis of clinical findings and morphological studies of bronchoalveolar lavage (BAL) and/or lung biopsy specimens before PCR testing. PCR was performed without knowledge of the diagnosis. PCR results were graded from "negative" to 3+ on the basis of intensity of the banding pattern. Forty-seven patients were enrolled in the study, including 18 with proven PCP and 29 with other conditions. PCR was positive at grade 1 or higher for all 18 patients with PCP (100% sensitivity), at grade 2 or higher for 13 patients (72.2% sensitivity), and at grade 1 or higher for 4 of the 29 control patients (specificity of 86.2%). If a grade 2 or higher was required for diagnosis, the specificity improved to 100%. Results were reproducible with testing of a second aliquot for 46 of 47 patients (97.8%). Our findings confirm that PCR is a sensitive and reproducible test for detection of P. carinii in BAL specimens. Problems with false-positive results for control patients, however, limit the applicability of this method.

AIDS-Related Opportunistic Infections↗
PubMed2000

Down-regulation of GATA-2 transcription during Pneumocystis carinii infection.

Differences in gene expression between Pneumocystis carinii-infected and noninfected rats were examined. Total RNA was isolated from homogenized rat lungs and then subjected to differential display with combinations of oligo(dT) and various arbitrary PCR primers. Approximately 50 differentially expressed bands were observed. Several of these DNA bands were isolated, reamplified, and cloned. The cloned DNA fragments were used as probes to perform Northern hybridization on RNA from P. carinii-infected and noninfected rat lungs. One clone was found to react with a 3-kb mRNA from noninfected but not from P. carinii-infected rat lung, suggesting that the gene represented by this clone was down-regulated during P. carinii infection. The nucleotide sequence of this clone was determined and found to be 97% homologous to the mouse GATA-2 transcription factor. In situ hybridization using RNA probes derived from this clone revealed that alveolar macrophages, resident lung monocytes, and bronchial epithelial cells express the GATA-2 gene in the lung.

Animals↗
PubMed2000

Regulation of rRNA transcription is remarkably robust: FIS compensates for altered nucleoside triphosphate sensing by mutant RNA polymerases at Escherichia coli rrn P1 promoters.

We recently identified Escherichia coli RNA polymerase (RNAP) mutants (RNAP beta' Delta215-220 and beta RH454) that form extremely unstable complexes with rRNA P1 (rrn P1) core promoters. The mutant RNAPs reduce transcription and alter growth rate-dependent regulation of rrn P1 core promoters, because the mutant RNAPs require higher concentrations of the initiating nucleoside triphosphate (NTP) for efficient transcription from these promoters than are present in vivo. Nevertheless, the mutants grow almost as well as wild-type cells, suggesting that rRNA synthesis is not greatly perturbed. We report here that the rrn transcription factor FIS activates the mutant RNAPs more strongly than wild-type RNAP, thereby compensating for the altered properties of the mutant RNAPs. FIS activates the mutant RNAPs, at least in part, by reducing the apparent K(ATP) for the initiating NTP. This and other results suggest that FIS affects a step in transcription initiation after closed-complex formation in addition to its stimulatory effect on initial RNAP binding. FIS and NTP levels increase with growth rate, suggesting that changing FIS concentrations, in conjunction with changing NTP concentrations, are responsible for growth rate-dependent regulation of rrn P1 transcription in the mutant strains. These results provide a dramatic demonstration of the interplay between regulatory mechanisms in rRNA transcription.

Carrier Proteins↗
PubMed2000

Typing of Histoplasma capsulatum isolates based on nucleotide sequence variation in the internal transcribed spacer regions of rRNA genes.

The nucleotide sequences of internal transcribed spacer (ITS) regions of rRNA genes of 24 isolates of Histoplasma capsulatum were examined. The results indicate that the sequences of ITS regions in different isolates are not identical. Sequence variations were found at 20 positions in the 496 bp that were sequenced. Ten different sequence patterns, designated types A through H, were observed when the sequences from the 24 isolates were aligned. Twelve isolates from Indianapolis were classified into four different types. Two isolates from New York belonged to type G. Three isolates from different cities were type F. The remaining six isolates were of different types.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Measuring facial expressions by computer image analysis.

Facial expressions provide an important behavioral measure for the study of emotion, cognitive processes, and social interaction. The Facial Action Coding System (Ekman & Friesen, 1978) is an objective method for quantifying facial movement in terms of component actions. We applied computer image analysis to the problem of automatically detecting facial actions in sequences of images. Three approaches were compared: holistic spatial analysis, explicit measurement of features such as wrinkles, and estimation of motion flow fields. The three methods were combined in a hybrid system that classified six upper facial actions with 91% accuracy. The hybrid system outperformed human nonexperts on this task and performed as well as highly trained experts. An automated system would make facial expression measurement more widely accessible as a research tool in behavioral science and investigations of the neural substrates of emotion.

Adult↗
PubMed1999

Intranasal immunization confers protection against murine Pneumocystis carinii lung infection.

To evaluate the feasibility of mucosal immunization against Pneumocystis carinii (Pc) experimental infection, female BALB/c mice were intranasally immunized three times with soluble Pc antigens plus cholera toxin fraction B (Pc-CTB); control groups received either Pc antigen, CTB, or phosphate-buffered saline (PBS) alone. Two weeks after the last immunization, five animals from each group were sacrificed, and cellular and humoral immune responses were evaluated. The remaining five mice were CD4 depleted using a monoclonal antibody against mouse CD4 and inoculated with viable Pc. Significantly higher specific lymphoproliferative responses from tracheobronchial lymph node cells, immunoglobulin M (IgM) and IgG antibody levels in serum, and bronchoalveolar lavage (BAL)-derived IgA antibody concentrations were observed in the Pc-CTB group of mice relative to control groups (P < 0.01). Five weeks after challenge, no Pc organisms were observed in the lung smears of the Pc-CTB group, while the animals receiving antigen, adjuvant, or PBS had progressively higher numbers of Pc microorganisms. By Western blot analysis, a strongly reactive 55- to 60-kDa antigen was recognized by BAL IgA and by serum IgG. In summary, mucosal immunization elicited specific cellular and humoral immune responses and protected against Pc lung infection after immunosuppression.

Administration, Intranasal↗
PubMed1998

RNA polymerase mutants that destabilize RNA polymerase-promoter complexes alter NTP-sensing by rrn P1 promoters.

Mutations in Escherichia coli rpoB or rpoC, selected for the ability to confer prototrophy on relA spoT strains, were found to affect transcription from rrn P1 promoters. Two mutant strains (beta RH454 and beta' delta 215-220) reduced transcription of rrn P1 core promoter-lacZ fusions but not of control promoter-lacZ fusions. Purified mutant RNAPs formed complexes with rrn P1 promoters that were much less stable than those formed by wild-type RNAP and required high concentrations of the initiating NTP for efficient rrn P1 transcription. The instability of the rrn P1 core promoter complexes with the mutant RNAPs and their altered regulatory properties support a recently proposed model for the control of rRNA transcription by changing concentrations of the initiating NTPs. We further suggest that destabilization of promoter complexes by the mutant RNAPs mimics effects of ppGpp, decreasing or increasing transcription depending on the kinetic properties of the specific promoter.

Adenosine Triphosphate↗
PubMed1998

Pneumocystis carinii mutations associated with sulfa and sulfone prophylaxis failures in AIDS patients.

BACKGROUND: Failures of prophylaxis against Pneumocystis carinii pneumonia (PCP) in AIDS patients do occur, but no evidence for drug resistance has yet been presented. OBJECTIVE: To determine whether mutations in the sulfa and sulfone drug target are associated with failure of prophylaxis using a sulfa-containing agent. METHODS: Portions of the gene for P. carinii dihydropteroate synthase (DHPS), the sulfa and sulfone target, from 27 patients (20 of whom had AIDS) diagnosed with PCP between 1976 and 1997 were amplified using polymerase chain reaction and sequenced. Seven of the 27 patients (all of whom had AIDS) were receiving sulfa or sulfone drugs as prophylaxis for PCP. RESULTS: Mutations were found at only two amino-acid positions and were significantly more common in patients who received sulfa/sulfone prophylaxis. Mutations were observed in five (71%) out of seven isolates from AIDS patients receiving sulfa/sulfone as prophylaxis compared with only two (15%) out of 13 specimens from AIDS patients who did not (P = 0.022). No mutations were seen in isolates from seven non-HIV-infected patients, none of whom were on prophylaxis. Mutations were only observed in specimens obtained in 1995-1997. CONCLUSIONS: Mutations in two amino-acid positions were significantly more common in AIDS patients with PCP who failed sulfa/sulfone prophylaxis. These amino acids appeared to be directly involved in both substrate and sulfa binding, based on homology to the Escherichia coli DHPS crystal structure. Thus, the results were consistent with the possibility that mutations in the P. carinii DHPS are responsible for some of the failures of sulfa/sulfone prophylaxis in AIDS patients.

AIDS-Related Opportunistic Infections↗
PubMed1998

Sequence polymorphisms in the Pneumocystis carinii cytochrome b gene and their association with atovaquone prophylaxis failure.

Atovaquone (Mepron, 566c80) is an effective agent against Pneumocystis carinii, which probably acts by binding to cytochrome b and inhibiting electron transport. To assess the possibility that atovaquone resistance might be developing, the genes for the cytochrome b from P. carinii sp. f. carinii and P. carinii sp. f. hominis were partially sequenced. Eight of 10 patient isolates had cytochrome b genes with the same amino acid sequence. The P. carinii cytochrome b genes from 2 of 4 patients who had atovaquone prophylaxis failure contained mutations resulting in amino acid changes in one of the ubiquinone (coenzyme Q) binding sites (Qo). These mutations are homologous to mutations in other microorganisms that confer resistance to similar inhibitors. Variations in the sequence of the P. carinii cytochrome b gene suggest but do not prove the development of drug resistance.

Amino Acid Sequence↗
PubMed1998

Current in vitro culture systems for Pneumocystis.

Although Pneumocystis continuous culture systems have not yet been developed, efficient short-term in vitro methods allowing the production of infectious forms of Pneumocystis can now be employed. The quality of the inoculum will influence the in vitro development of P. carinii. For this reason, efficient extraction and cryopreservation techniques are considered in this section. In vitro growth and limited passage were obtained by inoculating freshly extracted parasites onto fibroblast- or epithelial-like cell monolayers cultivated in ordinary tissue culture flasks, culture plates, microcarrier beads or other culture devices. Cultures were usually maintained in an atmosphere of 5% CO2 at 35-37 degrees C. The results obtained in these different systems were surprisingly similar: the number of parasites increased about 6-10 times within the first 3-4 days post-inoculation, then remained stationary until day 7-14 and decreased rapidly. If passages were attempted, the growth decreased gradually and no growth was recorded after 2-3 passages. Proof of the in vitro Pneumocystis attachment to feeder cells has been furnished by electron microscopy. Two currently used feeder cell culture systems were selected in this subchapter. The first system is a co-culture of monolayer lung epithelial-like cells with Pneumocystis. After trypsin treatment and passage of cells with attached parasites to culture bottles containing fresh medium, 3 or more new culture bottles can be plated. A 2-4-fold increase in parasite number can be obtained but, interestingly, cultured parasites were more infectious to the nude rat than freshly extracted lung parasites. In the second system, the spinner flask culture method, Pneumocystis is cultivated on cell coated microbeads in slow stirring vessels, in order to exploit the beads' huge surface where microorganisms can transiently adhere and grow and from where they can be easily detached by simply leaving the beads to settle down. This culture system has ensured 10(8)-10(9) viable trophozoites in each harvest after 7-10 days of slow stirring incubation.

Animals↗
PubMed1998

Evaluation of possible correlations between antifungal susceptibilities of filamentous fungi in vitro and antifungal treatment outcomes in animal infection models.

Nine isolates of filamentous fungi previously tested in 11 different laboratories for their susceptibilities to amphotericin B and itraconazole in vitro were injected intravenously into mice and guinea pigs, and responses to treatment with both agents were studied. The experiments were done in a single laboratory. Mean survival times, the percentages of animals surviving 12 days after infection, and culture results for samples of deep organs obtained postmortem were used as markers of antifungal efficacy. Because of variations in organism pathogenicity, interpretable test systems in vivo could not be established for Fusarium spp. in mice or guinea pigs or for Pseudallescheria boydii in mice, even with the use of immunosuppressive pretreatments. Among the infections that could be evaluated, some degree of response to the corresponding treatment in vivo was seen in animals infected with each of two Rhizopus arrhizus isolates susceptible to amphotericin B at < 0.5 microg/ml and Aspergillus spp. isolates susceptible to itraconazole at < 1.0 microg/ml. Conversely, no responses were apparent with infecting strains for which MICs were > or = 2 microg/ml (amphotericin B) or > or = 1 microg/ml (itraconazole). However, the limitations of the intravenous challenge systems studied mean that no firm conclusion relating MICs in vitro to the lowest effective doses in vivo could be drawn.

Amphotericin B↗