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Automated diagnostic systems with diverse and composite features for Doppler ultrasound signals.

In this paper, we present the automated diagnostic systems for Doppler ultrasound signals classification with diverse and composite features and determine their accuracies. We compared the classification accuracies of six different classifiers, namely multilayer perceptron neural network (MLP), combined neural network (CNN), mixture of experts (ME), modified mixture of experts (MME), probabilistic neural network (PNN), and support vector machine (SVM), which were trained on diverse or composite features. The present study was conducted with the purpose of answering the question of whether the automated diagnostic systems improve the capability of classification of ophthalmic arterial (OA) and internal carotid arterial (ICA) Doppler signals. Our research demonstrated that the SVM trained on composite feature and the MME trained on diverse features achieved accuracy rates which were higher than that of the other automated diagnostic systems.

Algorithms↗

Multiple model regression estimation.

This paper presents a new learning formulation for multiple model estimation (MME). Under this formulation, training data samples are generated by several (unknown) statistical models. Hence, most existing learning methods (for classification or regression) based on a single model formulation are no longer applicable. We describe a general framework for MME. Then we introduce a constructive support vector machine (SVM)-based methodology for multiple regression estimation. Several empirical comparisons using synthetic and real-life data sets are presented to illustrate the proposed approach for multiple model regression formulation.

Algorithms↗

Analysis of stage-specific and shared antigens derived from Rhipicephalus sanguineus by electrophoresis and western blotting.

We carried out an SDS-PAGE analysis of antigens of Rhipicephalus sanguineus using extracts of eggs (EE), larvae (LE), nymphs (NE), male salivary glands (MSGE), male midguts (MME), female salivary glands (FSGE) and female midguts (FME). Under non-reducing conditions a common band of about 205 kDa was observed. EE, LE and NE extracts showed groups of bands between 150 and 75 kDa. A protein pattern was observed in FSGE extract with a group of bands between 75 and 50 kDa and four bands between 15 and 6.5 kDa. In this case an apparently exclusive band of molecular weight about 25 kDa was observed. Under reducing conditions similarities between LE and NE extracts increased, separating from the EE pattern. On the other hand, we have determined the presence of stage-specific and common antigens on EE, LE, NE, MSGE, MME, FSGE and FME extracts of R.sanguineus by means of immunoblots using polyclonal sera of rabbits infested with larvae, nymphs or adults of this tick. EE extract was only recognized by the anti-larva sera. Higher reactivity was observed when the extracts were tested with anti-adult sera. In these experiments a very prominent band of molecular weight about 45 kDa was detected. This band was not observed under reducing conditions. Higher reactivity with anti-adult sera was observed against FSGE extract.

Animals↗

Bezafibrate suppresses rat antiglomerular basement membrane crescentic glomerulonephritis.

BACKGROUND: The immunoregulatory activity of ligands for peroxisome proliferator-activated receptors (PPARs) has been recently paid attention. The regulatory effect of bezafibrate (BZF), a ligand for PPARalpha on glomerulonephritis was investigated using a rat anti-glomerular basement membrane (GBM) glomerulonephritis model. METHODS: The effect on development of anti-GBM glomerulonephritis was examined by treatment with BZF from day -7 to day 7 after intravenous injection of rabbit anti-GBM serum into Wistar Kyoto (WKY) rats. The therapeutic efficacy after onset of the glomerulonephritis was also checked by treatment with BZF from day 3 to 7. On day 7, the condition was evaluated histologically. The expression of a tissue injury molecule, macrophage metalloesterase (MME), was measured by Northern blot analysis. The suppressive effect on immune cells was assessed by proliferation assay with mitogen-stimulated rat spleen cells. RESULTS: Histopathologic changes induced by anti-GBM in rats treated with BZF (day -7 to day 7) were markedly suppressed in a dose-dependent fashion. Infiltration of ED-1+ macrophages in glomeruli, proteinuria, and mRNA expression of MME in kidneys were diminished in parallel with histologic improvement. Moreover, the disease activity was also attenuated even by the treatment after onset of the glomerulonephritis (day 3 to 7). The mitogen-induced proliferation of spleen cells was down-regulated at concentrations of BZF, which were equivalent to those in sera of BZF-treated rats. CONCLUSION: BZF markedly suppresses the activity of rat anti-GBM crescentic glomerulonephritis. Fibrates might serve as a therapeutic option for crescentic glomerulonephritis.

Animals↗

Mesangial accumulation of GA-pyridine, a novel glycolaldehyde-derived AGE, in human renal disease.

BACKGROUND: Advanced glycation end products (AGEs) contribute to diabetic and atherosclerotic end-organ damage, but the mechanisms of AGE-formation and AGE-induced damage are unclear. Glycolaldehyde (GA) is a Maillard-reaction intermediate and can be formed by reaction of L-serine with the myeloperoxidase-system. GA reacts with proteins to form AGEs, such as GA-pyridine, which is specific for protein modification by GA. GA-pyridine accumulates in human atherosclerotic lesions. As atherosclerosis and progressive glomerulosclerosis share many similarities, we hypothesized that GA-pyridine accumulates in renal diseases, especially those with prominent mesangial involvement. METHODS: Paraffin-embedded renal biopsies from 55 patients with various renal diseases, as well as control tissue, obtained from the unaffected part of kidneys from 10 patients with renal cell carcinoma were immunohistochemically stained with a monoclonal antibody directed against GA-pyridine and were scored semiquantitatively. Additional sections were scored for mesangial matrix expansion (MME) and focal glomerular sclerosis (FGS). RESULTS: In normal human kidneys, GA-pyridine was mainly localized in tubular epithelial cells, but not in the glomerular mesangium. Significant mesangial GA-pyridine accumulation was found in disorders with mesangial involvement as a common denominator. In contrast, mesangial GA-pyridine accumulation was less prominent in renal diseases without prominent mesangial involvement. Moreover, mesangial GA-pyridine accumulation was more pronounced in kidneys with higher MME and FGS scores across the different diagnoses. CONCLUSION: GA-pyridine accumulates in the mesangium in human renal disease, in particular in disorders with mesangial involvement. Further studies should elucidate whether mesangial GA-pyridine plays a role in the progression of glomerular damage.

Acetaldehyde↗

Molecular ecological analysis of the succession and diversity of sulfate-reducing bacteria in the mouse gastrointestinal tract.

Intestinal sulfate-reducing bacteria (SRB) growth and resultant hydrogen sulfide production may damage the gastrointestinal epithelium and thereby contribute to chronic intestinal disorders. However, the ecology and phylogenetic diversity of intestinal dissimilatory SRB populations are poorly understood, and endogenous or exogenous sources of available sulfate are not well defined. The succession of intestinal SRB was therefore compared in inbred C57BL/6J mice using a PCR-based metabolic molecular ecology (MME) approach that targets a conserved region of subunit A of the adenosine-5'-phosphosulfate (APS) reductase gene. The APS reductase-based MME strategy revealed intestinal SRB in the stomach and small intestine of 1-, 4-, and 7-day-old mice and throughout the gastrointestinal tract of 14-, 21-, 30-, 60-, and 90-day-old mice. Phylogenetic analysis of APS reductase amplicons obtained from the stomach, middle small intestine, and cecum of neonatal mice revealed that Desulfotomaculum spp. may be a predominant SRB group in the neonatal mouse intestine. Dot blot hybridizations with SRB-specific 16S ribosomal DNA (rDNA) probes demonstrated SRB colonization of the cecum and colon pre- and postweaning and colonization of the stomach and small intestine of mature mice only. The 16S rDNA hybridization data further demonstrated that SRB populations were most numerous in intestinal regions harboring sulfomucin-containing goblet cells, regardless of age. Reverse transcriptase PCR analysis demonstrated APS reductase mRNA expression in all intestinal segments of 30-day-old mice, including the stomach. These results demonstrate for the first time widespread colonization of the mouse intestine by dissimilatory SRB and evidence of spatial-specific SRB populations and sulfomucin patterns along the gastrointestinal tract.

Aging↗

A high-throughput method for cloning and sequencing human immunodeficiency virus type 1 integration sites.

Integration of retroviral DNA is nonspecific and can occur at many sites throughout chromosomes. However, the process is not uniformly distributed, and both hot and cold spots for integration exist. The mechanism that determines target site specificity is not well understood. Because of the nonspecific and widespread nature of integration, studies analyzing the mechanism and factors that control target site selection require the collection and analysis of a large library of human immunodeficiency virus type 1 (HIV-1) proviral clones. Such analyses are time-consuming and labor-intensive using conventional means. We have developed an efficient and high-throughput method of sequencing and mapping a large number of independent integration sites in the absence of any selection or bias. The new assay involves the use of a modified HIV-1 (NL-Mme) containing a type IIS restriction site, MmeI, at the right end of viral DNA. Digestion of genomic DNA from NL-Mme-infected cells generated viral DNA-containing fragments of a discrete size. Subsequent ligation-mediated PCR yielded short integration site fragments termed Int-tags, which were concatemerized for determining multiple integration sites in a single sequencing reaction. Analysis of chromosomal features and sequence preference associated with integration events confirmed the validity of the new high-throughput assay. The assay will aid the effort in understanding the mechanisms of target site selection during HIV-1 DNA integration, and the described methodology can be adapted easily to integration site studies involving other retroviruses and transposons.

Cell Line↗

Linkage and microarray analyses of susceptibility genes in ACI/Seg rats: a model for prostate cancers in the aged.

ACI/Seg (ACI) rats develop prostate cancers spontaneously with aging, similar to humans. Here, to identify genes involved in prostate cancer susceptibility, we did linkage analysis and oligonucleotide microarray analysis. Linkage analysis was done using 118 effective rats, and prostate cancer susceptibility 1 (Pcs1), whose ACI allele dominantly induced prostate cancers, was mapped on chromosome 19 [logarithm of odds (LOD) score of 5.0]. PC resistance 1 (Pcr1), whose ACI allele dominantly and paradoxically suppressed the size of prostate cancers, was mapped on chromosome 2 (LOD score of 5.0). When linkage analysis was done in 51 rats with single or no macroscopic testicular tumors, which had larger prostates and higher testosterone levels than those with bilateral testicular tumors, Pcs2 and Pcr2 were mapped on chromosomes 20 and 1, respectively. By oligonucleotide microarray analysis with 8,800 probe sets and confirmation by quantitative reverse transcription-PCR, only two genes within these four loci were found to be differentially expressed >1.8-fold. Membrane metalloendopeptidase (Mme), known to inhibit androgen-independent growth of prostate cancers, on Pcr1 was expressed 2.0- to 5.5-fold higher in the ACI prostate, in accordance with its paradoxical effect. Cdkn1a on Pcs2 was expressed 1.5- to 4.5-fold lower in the ACI prostate. Additionally, genes responsible for testicular tumors and unilateral renal agenesis were mapped on chromosomes 11 and 14, respectively. These results showed that prostate cancer susceptibility of ACI rats involves at least four loci, and suggested Mme and Cdkn1a as candidates for Pcr1 and Pcs2.

Animals↗

Matrix metalloproteinase expression and production by alveolar macrophages in emphysema.

The aim of this study was to examine the hypothesis that alveolar macrophages represent a significant source of matrix-degrading proteinases in the emphysematous lung. Macrophages from bronchoalveolar lavage fluid of 10 patients with emphysema and 10 normal volunteers were maintained in vitro for 24 h and assessed semiquantitatively for mRNA transcript levels of the matrix metalloproteinases (MMPs) gelatinases A and B, macrophage metalloelastase (MME), and interstitial collagenase. Release of these MMPs into the culture medium and secretion of neutrophil elastaselike activity was also assessed. Elevated levels of mRNA transcripts for gelatinase B (p < 0.0005) and interstitial collagenase (p < 0.0005) were observed in macrophages from emphysematous patients. Increased collagenase (p < 0.01) and neutrophil elastaselike activities (p < 0.001) were also measured in conditioned medium from patient macrophages. With gelatinase B, complexed forms of the enzyme were secreted by patient but not by control macrophages. No difference in transcript levels of gelatinase A or MME was observed between patient and control samples, and neither enzyme was detected in macrophage-conditioned media from either group. These results directly demonstrate that alveolar macrophages from the emphysematous lung produce elevated quantities of matrix-degrading enzymes with both elastolytic and collagenolytic activities.

Adult↗

Men who advertise for sex.

This content analysis of 1,111 paid ads in the Advocate identifies 17 self-descriptive categories in the "Personals" (PER) and "Models, Masseurs, and Escorts" (MME) sections of the "Trader Dick" supplement. Advertisers place primary emphases on sex and masculinity. Among MME, youthfulness, handsomeness, and sexiness are important, promoting versatility in place of specificity when mentioning sexual acts. PER advertisers, however, indicate concerns about age, race, and finding lovers. They also detail specific sexual interests and reject a variety of unacceptable behaviors.

Adult↗

Photodynamic inactivation of the dermatophyte Trichophyton rubrum.

Dermatophytes are fungi that can cause infections (known as tinea) of the skin, hair and nails because of their ability to use keratin. Superficial mycoses are probably the most prevalent of infectious diseases worldwide. One of the most distinct limitations of the current therapeutic options is the recurrence of the infection and duration of treatment. The present study shows that Trichophyton rubrum in suspension culture is susceptible to photodynamic treatment (PDT), a completely new application in this area. T. rubrum could be effectively killed with the use of the light-activated porphyrins deuteroporphyrin monomethylester (DP mme) and 5,10,15-tris(4-methylpyridinium)-20-phenyl-[21H,23H]-porphine trichloride (Sylsens B). The photodynamic efficacy was compared with that of some other photosensitizers that are well known in the field of PDT: the porphyrins deuteroporphyrin and hematoporphyrin, the drug Photofrin and several phthalocyanines. It was demonstrated that with the use of broadband white light, the phthalocyanines and Photofrin displayed a fungistatic effect for about 1 week, whereas all the porphyrins caused photodynamic killing of the dermatophyte. Sylsens B was the most effective sensitizer and showed no dark toxicity; therefore, in an appropriate formulation, it could be a promising candidate for the treatment of various forms of tinea. For Sylsens B and DP mme, which displayed the best results, a concentration-dependent uptake by T. rubrum was established.

Arthrodermataceae↗

Recombinant gilthead seabream (Sparus aurata) insulin-like growth factor-I: subcloning, expression in Escherichia coli, purification and characterization.

Gilthead seabream (Sparus aurata) insulin-like growth factor-I (gsIGF-I) cDNA coding for the mature protein was cloned in a pGEM-3Z vector, and then transferred into prokaryotic expression vector pET-11a and expressed in Escherichia coli BL21(DE3) cells upon induction with isopropyl thiogalactoside. The expressed protein contained within the inclusion-body pellet was solubilized in 4.5 M urea, refolded for 24 h at pH 11.3 in the presence of catalytic amounts of cysteine and purified to over 98% purity, as a monomeric methionyl-gsIGF-I. Amino acid composition and N-terminal sequence confirmed the identity to be the predicted protein. Binding assays of the 125I-gsIGF-I to gilthead seabream or carp (Cyprinus carpio) sera resulted in high specific binding, indicating the existence of one or more IGF-binding proteins. In binding experiments to crude gilthead seabream brain homogenate, using human (h) IGF-I as a ligand, the respective IC50 value of hIGF-I was about fourfold lower than that of gsIGF-I. Recombinant gsIGF-I exhibited mitogenic activity in a mouse mammary gland-derived MME-L1 cell line which was approximately 200-fold lower than that of hIGF-1. Binding experiments to intact MME-L1 cells suggests that this difference most likely results from a correspondingly lower affinity for IGF-I receptor in these cells. In contrast, the activities of gsIGF-I and hIGF-I measured by 35S uptake by gill arches from the goldfish (Carassius auratus) were identical, indicating that the recombinant gsIGF-I is biologically active.

Animals↗

[The disgrace of Antoine Daquin, first physician of Louis XIV (1693)].

Antoine Daquin, Principal Physician of Louis XIV and Earl of Jouy-en-Josas, was born in Paris. He was the son of Louis-Henri Daquin, Physician to Queen Marie de Médicis; his paternal grandfather, born in the Jewish religion, became converted to catholicism at Aquino, in Italy, whence his name d'Aquin, then Daquin. A. Daquin studied to be a doctor at Montpellier and graduated on 18 May 1648. He married Marguerite Gayant, Antoine Vallot's niece, Antoine Vallot being the Principal Physician of Louis XIV. This relationship permitted him to get the position of Principal Physician of the Queen, then, after Vallot's death, to succeed him, on 18 April 1672, as Principal Physician of the King. The kindliness of the King's mistress, Mme de Montespan, helped him in that appointment. Daquin was a good doctor, he turned out awkward: "great courtier, but rich, miser, grasping, wanting to establish his family anyway" said the Duc de Saint-Simon. He dared ask the King for the Archbishopric of Tours for his son: "it was the rock on which he broke up" said again Saint-Simon. On 2 November 1693, the comte de Pontchartrain came to his home by order of the King, to tell him, he was ordered to retire from Court without delay. It was forbidden him to come back or to write to the King. Guy-Crescent Fagon was designated "Premier Médecin" instead of him; but Fagon had worked at the undoing of Daquin, with a view to robbing him of his position, with the complicity of the King's new mistress, Mme de Maintenon. After his disgrace, Daquin retired probably to Moulins; he died obscurely in Vichy, on 17 May 1696. Today, Daquin is regarded as a victim of intrigues of Court, which explains his celebrity.

Famous Persons↗

Dr. Nobuo Yamada's whole life, dead due to his radioactive studies at the Radium Institute (Part 2): in celebration of the 100-year anniversary of the discovering radium, 1898-1998.

On the occasion of the 100th anniversary of the discovery of radium by M. & Mme. Curie, commemorative lecture meetings were held in Japan in 1998 as follows. 1) The 42nd Symposium on Radiochemistry was held in Sendai on September 18. Dr. M. Sakanoue, Professor Emeritus Kanazawa University, presented a commemorative lecture entitled "Collaborative Research done by Irene Curie and Nobuo Yamada." He explained an outline of the studies on the measurement of long-range particles emitted by various radioactive substances such as polonium, radium and thorium. In addition to his lecture, I made a comment on the curriculum vitae of Dr. N. Yamada. 2) On October 24, another commemorative lecture meeting was held in Tokyo. At this meeting, Helene Langevin-Joliot, daughter of Irene Joliot-Curie presented a lecture on whole life of M. & Mme. Curie as a guest speaker. After meeting ended, I had the opportunity to talk with her personally. I have been investigating references describing the cause of death of Dr. Nobuo Yamada and found the following. The inadequacy of an apparatus for protection from radioactivity in the 1920s and reference to the death of Dr. Nobuo Yamada specifically were described in an article written by Dr. S. Iimori and in a nonograph written by Dr. M. Furukawa. The tragedy of scientists who suffered severe radiation syndrome during experiments at the Radium Institute was described in a biography of Marie Curie written by Susan Quinn.

Academies and Institutes↗

China strives to limit population to 1.294 billion by 2000.

Mme. Peng Peiyun, minister of the State Family Planning Commission, said that China must strive to limit its total population to 1.294 billion by the end of the century as set by the 8th 5-Year Population Plan and the 10-Year Population Program. The average annual net increase of population in the country in this decade will need to drop to 15.1 million with an annual rate of natural increase of no more than 12.49/1000. According to these goals, the total fertility rate of women at childbearing age must be reduced from 2.3 in 1990 to 2.1 in 1995 and continue to decline below the present average in developed countries. These figures were announced at the National Conference for Commending Advanced Units and Model Individuals for Publicity on Family Planning held in Beijing on September 25, 1991. It is very arduous to reach the goals, admitted Minister Peng, because: First,China has a large population base and is at present confronted with the 3rd baby boom since 1949. There will be 19 million planned births each year during the 8th 5-Year Plan (1991-95). Second, the implementation of the family planning program is uneven in the country. During the 1980s, the total fertility rate of urban women was kept below 1.5 while that of rural women was around 2.8. The 1990 national population census shows that the proportion of 3rd and higher parity births is still as high as 19.32%. Facing the present grave situation of population growth, we have to increase the emphasis on publicity and education about population and family planning to better facilitate implementation of the family planning program. At the conference 365 advanced units and 485 model individuals were commended. Mr. Wang Renzhi, head of the Publicity Department of the Party's Central Committee, and Mme. Peng Peiyun attended the awarding ceremony for commendation.

Asia↗

Heterogeneity and multiple expression of intermediate filament proteins, S-100 protein and neuron specific enolase in skin mixed tumor.

Intermediate filament proteins, keratin (KL1, PKK1, K8.12) and vimentin, S-100 protein alpha and beta subunits and neuron specific enolase were evaluated immunohistochemically to determine their distribution patterns in the tumor components of mixed tumor of skin. Keratin proteins were distributed widely in tumor epithelial cells or modified myoepithelial (MME) or neoplastic myoepithelial (NME) cells. Luminal cells of the tubulo-ductal structure of the tumor mass showed positive staining of KL1 and PKK1 keratins and an infrequently positive reaction of MoAb K8.12. The outer or basal tumor cells were characterized by coexpression of K8.12 keratin, vimentin, S-100 protein and infrequently neuron specific enolase reactivity. Heterogeneity of keratin distribution was seen in tumor epithelial cells. MME cells or NME cells of skin mixed tumor showed coexpression of keratin and vimentin, and multiple expression of intermediate filament proteins, S-100 protein and neuron specific enolase. Hyaline and chondroid changed cells stained intensely to vimentin and S-100 proteins, as well as to neuron specific enolase. The authors evaluate the histogenesis of skin mixed tumor in relation to epithelial and myoepithelial cells of the sweat gland and their immunohistochemical findings.

Adenoma, Sweat Gland↗

[Rhabdomyoma of the interventricular septum in a one-day-old newborn infant. Echocardiographic diagnosis].

A case of interventricular septal rhabdomyoma in a one day-old newborn is presented. The newborn was moderately cyanosed. A 3/6 systolic murmur in basal area was present. An electrocardiogram showed the features of Wolff-Parkinson-White syndrome. A chest x-ray showed distinct cardiomegaly. M-Mode (MME) and Two-dimensional echocardiography (2DE) identified an interventricular septal mass within left ventricle and suggested the presence of left ventricular outflow obstruction. We emphasize the usefulness of MME and 2DE in accurately diagnosing intramural ventricular tumors in newborns.

Echocardiography↗

Cis and trans requirements for stable episomal maintenance of the BPV-1 replicator.

Papillomavirus genomes are maintained as multicopy nuclear plasmids in transformed cells. To address the mechanisms by which the viral DNA is stably propagated in the transformed cells, we have constructed a cell line CH04.15 expressing constitutively the viral proteins E1 and E2, that are required for initiation of viral DNA replication. We show that these viral proteins are necessary and sufficient for stable extrachromosomal replication. Using the cell line CH04.15, we have shown that the bovine papillomavirus-1 (BPV-1) minimal origin of replication (MO) is absolutely necessary, but is not sufficient for stable extrachromosomal replication of viral plasmids. By deletion and insertion analysis, we identified an additional element (minichromosome maintenance element, MME) in the upstream regulatory region of BPV-1 which assures stable replication of the MO-containing plasmids. This element is composed of multiple binding sites for the transcription activator E2. MME appears to function in the absence of replication but requires E1 and E2 proteins for activity. In contrast to, for example, Epstein-Barr virus oriP, stably maintained BPV-1 plasmids are not subject to once-per-cell cycle replication as determined by density labelling experiments. These results indicate that papillomavirus episomal replicators replicate independently of the chromosomal DNA of their hosts.

Animals↗