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PubMed1980

Penile flow index utilizing a Doppler pulse wave analysis to identify penile vascular insufficiency.

A Doppler ultrasound probe was used in 42 men to evaluate penile circulation. Twenty-six patients had confirmation of vascular anatomy by pelvic arteriography. The average penile acceleration (peak velocity over pulse rise time) relative to the radial artery acceleration was expressed as the penile flow index. Eleven potent men had a penile flow index of 3.4 plus or minus 0.4 standard error, while 13 impotent men with vascular disease on arteriography had a penile flow index of 21.7 plus or minus 5 standard error (p less than 0.01). Patients with intermediate penile flow index values had variable degrees of erectile failure. This relatively simple, non-invasive technique identifies a vascular component of impotence, thus aiding in the selection of appropriate management.

Erectile Dysfunction↗
PubMed2004

Antimicrobial susceptibility among community-acquired respiratory tract pathogens in the USA: data from PROTEKT US 2000-01.

OBJECTIVES: The PROTEKT US surveillance program (Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin in the United States) commenced in 2000 to document the emergence and spread of antimicrobial resistance among respiratory tract pathogens in the United States. METHODS: During 2000-2001, 206 centers from 154 cities/metropolitan areas collected 16,727 clinical isolates (Streptococcus pneumoniae, n=10103, Streptococcus pyogenes, n=3918, Haemophilus influenzae, n=2706). RESULTS: Among S. pneumoniae isolates, 38.9% showed decreased susceptibility to penicillin (12.5% intermediate, 26.4% resistant) with marked geographical variability. The erythromycin resistance rate was 31.0% and highly correlated with penicillin resistance. The rate of fluoroquinolone resistance was 0.8%. Telithromycin was nearly uniformly active against S. pneumoniae (MIC(90) 0.5 mg/l). All isolates of S. pyogenes were penicillin-susceptible, 5.5% were resistant to erythromycin. Telithromycin minimum inhibitory concentrations (MICs) were lower than clindamycin and macrolide MICs against S. pyogenes (MIC(90) 0.03 mg/l versus 0.25 mg/l and 0.12 mg/l, respectively). 28.3% of H. influenzae isolates produced beta-lactamase. Telithromycin activity versus H. influenzae was not affected by beta-lactamase production. CONCLUSIONS: The PROTEKT US study confirms the widespread prevalence of antimicrobial resistance among common bacterial respiratory pathogens in the US, and re-affirms the importance of continued surveillance to guide optimum empiric therapy for patients with Community-acquired respiratory tract infections (CARTIs). The new ketolide, telithromycin, maintained potent activity against study isolates in vitro and offers promise for the effective treatment of CARTIs.

Anti-Bacterial Agents↗
PubMedDate not supplied

Stability and electronic properties of nitrogen nanoneedles and nanotubes.

The electronic structures and stability of nitrogen nanostructures, nanotubes, and fiberlike nanoneedles of various diameters, formed by units N2m (m = 2-6), were studied by quantum chemistry computational modeling methods. The geometrical structures with various cross-sections and terminal units, their energetic stability, and their rather peculiar electron density distributions were investigated. The tightest nitrogen nanoneedle (NNN) studied theoretically in this work is the structure (N4n with D2h symmetry, whereas the nitrogen nanotube (NNT) with the largest diameter discussed here is the structure (N12)n with D2 symmetry. These families of NNNs and NNTs can be considered as nanostructures not only for potential applications as devices in nanotechnology or as possible scaffold structures but also as ligands in synthetic chemistry and high-energy density materials (HEDMs). As a consequence of the lone-pair electrons present around the walls of these NNNs and NNTs, these nitrogen nanostructures and the nitrogen nano-bundles (NNB) formed by aligning and combining them using intermediate carbon atoms, can have highly variable electronic properties controlled by the changing charge environment. In particular, for extended systems based on the units studied here, the band gaps of each of these systems can be affected greatly by the local charge of the environment.

Journal Article↗
PubMed2005

Cellular and complement-dependent cytotoxicity of Ep-CAM-specific monoclonal antibody MT201 against breast cancer cell lines.

MT201 is a fully human monoclonal IgG1 antibody with moderate affinity for epithelial cell adhesion molecule (Ep-CAM) being clinically developed for the treatment of carcinomas. Like many other clinically validated IgG1 monoclonal antibodies, MT201 primarily acts by antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). Here, we analysed ADCC and CDC induced by MT201 and, as reference, trastuzumab against a panel of nine human breast cancer cell lines expressing distinct surface levels of Ep-CAM and human epithelial growth factor receptor type 2 antigen. Maximal cell lysis by ADCC by MT201 and trastuzumab in the presence of peripheral mononuclear cells did not significantly differ when averaged over the nine cell lines, but showed marked differences with respect to individual cell lines. The extent of cell lysis at intermediate surface target density was highly variable, suggesting a dominant influence of other susceptibility factors. Only one breast cancer cell line was eliminated via CDC, but only by MT201. Resistance to CDC appeared to correlate with high expression levels of complement resistance factors. Our present data as well as recent data on the prevalence and prognostic relevance of Ep-CAM expression in metastatic breast cancer suggest that Ep-CAM-specific monoclonal IgG1 antibodies may have a significant therapeutic potential in the treatment of breast cancer.

Animals↗
PubMed1985

Variability of lip and jaw movements in children and adults: implications for the development of speech motor control.

The development of speech motor skill was studied by measuring the variability of lower lip and jaw movements. Groups of five adults, and children at ages 4, 7, and 10 years produced [mae] and [bae] 20 times each. The duration of lip-opening movements, jaw-opening movements, lip-open postures, jaw-open postures, and the timing between the onset of lower lip opening and jaw opening decreased in variability between the child and adult groups. No significant differences were observed in the variability of these measures across the child groups. The variability of lower lip displacement decreased significantly between the 4-year-old and 7-year-old groups, but not between any other age groups. Jaw displacement variability did not change significantly between any groups. No significant differences in variability were found between [bae] and [mae]. It is hypothesized that different developmental motor processes affect the variability of speech movements at early, intermediate, and older ages.

Age Factors↗
PubMed2002

11Beta-hydroxysteroid dehydrogenase 1 expression in squamous cell carcinomas of the head and neck.

11Beta-hydroxysteroid dehydrogenase 1 (11beta-HSD1) has been identified as a major detoxification enzyme of one of the most potent tobacco smoke-derived carcinogens, NNK. If not metabolized by 11beta-HSD1, activation of NNK by cytochrome p450 mono-oxidase 2D6 (CYP2D6) results in an electrophile intermediate responsible for DNA damage. Interindividual variability in the expression of 11beta-HSD1 and CYP2D6 has been found to influence the susceptibility to lung cancer. The aim of this study was to compare 11beta-HSD1 mRNA expression and CYP2D6 metabolizer status in pharyngeal tissues of patients with oropharyngeal carcinoma and controls. In 20 patients with oropharyngeal cancer and 15 non-smoking controls, the 11beta-HSD1 mRNA expression was assessed with RT-PCR. The frequency of genetic polymorphisms of the CYP2D6 gene was assessed using RFLP. It was found that 11beta-HSD1 mRNA is expressed in human pharyngeal mucosa. It is upregulated in mucosa exposed to tobacco smoke. In tumour tissues, 11beta-HSD1 expression was significantly lower than in non-affected mucosa. The frequency distribution of CYP2D6 gene polymorphisms was similar in patients and controls. Chronic tobacco abuse results in 11beta-HSD1 enzyme induction. A reduction of 11beta-HSD1 expression in tumour tissues could be a consequence of malignantly transformed cells. It remains unclear if the lower 11beta-HSD1 expression gives rise to an increased rate of additional mutations.

11-beta-Hydroxysteroid Dehydrogenase Type 1↗
PubMed2005

Iodotyrosine deiodinase is the first mammalian member of the NADH oxidase/flavin reductase superfamily.

The enzyme responsible for iodide salvage in the thyroid, iodotyrosine deiodinase, was solubilized from porcine thyroid microsomes by limited proteolysis with trypsin. The resulting protein retained deiodinase activity and was purified using anion exchange, dye, and hydrophobic chromatography successively. Peptide sequencing of the final isolate identified the gene responsible for the deiodinase. The amino acid sequence of the porcine enzyme is highly homologous to corresponding genes in a variety of mammals including humans, and the mouse gene was expressed in human embryonic kidney 293 cells to confirm its identity. The amino acid sequence of the deiodinase suggests the presence of three domains. The N-terminal domain provides a membrane anchor. The intermediate domain contains the highest sequence variability and lacks homology to structural motifs available in the common databases. The C-terminal domain is highly conserved and resembles bacterial enzymes of the NADH oxidase/flavin reductase superfamily. A three-dimensional model of the deiodinase based on the coordinates of the minor nitroreductase of Escherichia coli indicates that a Cys common to all of the mammal sequences is located adjacent to bound FMN. However, the deiodinase is not structurally related to other known flavoproteins containing redox-active cysteines or the iodothyronine deiodinases containing an active site selenocysteine.

Amino Acid Sequence↗
PubMed2000

The rate of progression to AIDS is independent of virus dose in simian immunodeficiency virus-infected macaques.

Of the viral factors that are proposed to influence the rate of progression to AIDS, the role of infectious dose remains unresolved. Intravenous infection of outbred Macaca mulatta with various doses of simian immunodeficiency virus isolate 8980 (SIV(8980)) revealed an endpoint from which an infectious dose 50 (ID(50)) was defined. In the six infected animals, the time to develop AIDS was variable with a spectrum of rapid, intermediate and slow progressors. High and sustained plasma viraemia with marked loss of CD4(+) T-cells was a distinguishing feature between rapid versus intermediate and slow progressors. Animals that received the highest doses did not develop the highest sustained viral loads, nor did they progress more rapidly to disease. Similarly, animals infected with lower doses did not uniformly develop lower viral loads or progress more slowly to AIDS. Furthermore, compiled data from more than 21 animals infected with different doses of the same virus administered by the same route failed to reveal any correlation of infectious dose with survival. Indeed, host factors of these outbred animals, rather than dose of the initial inoculum, were probably an important factor influencing the rate of disease progression in each individual animal. Comparison of animals infected with SIV(B670), from which SIV(8980) was derived, revealed marked differences in disease progression. Clearly, although dose did not influence viral loads nor disease progression, the virulence of the initial inoculum was a major determinant of the rate of progression to AIDS.

Animals↗
PubMed1976

Immunological heterogeneity among the M-associated protein antigens of group-A streptococci.

Different serotypes of group-A streptococci share common antigens that are closely associated with the type-specific determinant of M protein. By the use of selected human sera containing antibody to these M-associated antigens, we have shown that group-A streptococci can be divided into three categories. The majority of the opacity-factor-negative respiratory serotypes possess a shared M-associated antigen or antigens, to which high titres of antibody are common in patients with rheumatic fever, or patients recovering from upper respiratory infections with certain opacity-factor-negative serotypes. The antibody in these sera has a demonstrable but limited affinity for the M-associated antigens of strains belonging to a second category of M types, the majority of which are opacity-factor-positive serotypes of "throat" or "skin" origin. A third group, consisting mainly of opacity-factor-negative pyoderma serotypes, gave variable results and seemed to be intermediate between the other two categories. Complement-fixation-inhibition tests and absorption studies showed a marked degree of cross-reactivity between the M-associated antigens of the three categories.

Acute Disease↗
PubMed2004

Non-Markovian rotating unstable processes driven by Gaussian colored noise.

In this paper the statistical properties of the mean passage time distribution are used to characterize the decay process of non-Markovian rotating unstable processes driven by Gaussian colored noise and subjected to the influence of a constant external force. The time characterization will be linear and studied in two limiting cases: large and intermediate times. General systems of two variables are studied. In both schemes we show that, for small correlation time of the noise, the non-Markovian effects are taken into account by an effective noise intensity. To compare qualitatively the non-Markovian time scale with respect to the Markovian case, we apply those results to determine the detection bandwidth of a large external signal in a laser system.

Journal Article↗
PubMed2006

Incipience of quantum chaos in the Jahn-Teller model.

We studied complex spectra of a two-level electron system coupled to two phonon (vibron) modes represented by the product of E and e Jahn-Teller model. For particular rotation quantum numbers we found a coexistence of up to three regions of the spectra: (i) the dimerized region of long-range-ordered (extended) pairs of oscillating levels, (ii) the short-range-ordered (localized) "kink lattice" of avoiding levels, and (iii) the intermediate region of kink nucleation with variable range of ordering. This structure appears above a certain critical line as a function of interaction strength. The level clustering and level avoiding generic patterns reflect themselves in several intermittent regions between up to three branches of spectral entropies. Linear scaling behavior of the widths of level curvature probability distributions provides the conventionally adopted indication for the presence of quantum chaos. Level spacing probability distributions show peculiarities of the partial (for fixed quantum angular momentum) as well as of the cumulative (all angular momenta) case. The clustering of levels with two and three dominant spacings at fixed angular momenta causes notable deviations of the cumulative distributions from the Poissonian one.

Journal Article↗
PubMed1979

Photosynthetic carbon metabolism in seagrasses C-labeling evidence for the c(3) pathway.

The delta(13)C values of several seagrasses were considerably less negative than those of terrestrial C(3) plants and tended toward those of terrestrial C(4) plants. However, for Thalassia hemprichii (Ehrenb.) Aschers and Halophila spinulosa (R. Br.) Aschers, phosphoglycerate and other C(3) cycle intermediates predominated among the early labeled products of photosynthesis in (14)C-labeled seawater (more than 90% at the earliest times) and the labeling pattern at longer times was brought about by the operation of the C(3) pathway. Malate and aspartate together accounted for only a minor fraction of the total fixed label at all times and the kinetic data of this labeling were not at all consistent with these compounds being early intermediates in seagrass photosynthesis. Pulse-chase (14)C-labeling studies further substantiated these conclusions. Significant labeling of photorespiratory intermediates was observed in all experiments. The kinetics of total fixation of label during some steady-state and pulse-chase experiments suggested that there may be an intermediate pool of inorganic carbon of variable size closely associated with the leaves, either externally or internally. Such a pool may be one cause for the C(4)-like carbon isotope ratios of seagrasses.

Journal Article↗
PubMed2006

Does competitive divergence occur if assortative mating is costly?

Most models of sympatric speciation have assumed that assortative mating has no costs. A few studies, however, have shown that the costs for being choosy can prevent such speciation. Here, we investigate the role of the strength of assortment and of the costs for being choosy for a simple genetic model of a single ('magic') trait that mediates both intraspecific competition for a continuum of resources and assortative mating, which is induced by choosy females who preferentially mate with males of similar phenotype. Choosiness may be costly if it is difficult to find a mating partner. Such magic trait models are considered to be most conducive of sympatric speciation. We consider a sexually reproducing population of haploid individuals that is density regulated. The trait is determined by a single locus with multiple alleles. The strength of stabilizing selection (caused by a unimodal resource distribution), the strength of competition, the degree of assortment and the costs for being choosy are independent parameters. We investigate analytically and numerically how these parameters determine the equilibrium and stability structure. In particular, we identify conditions under which no polymorphism at all is maintained as well as conditions under which strong competitive divergence occurs, or the population even splits into two reproductively isolated classes of highly diverse phenotypes. If costs are absent or moderate, genetic variability tends to be minimized at intermediate strengths of assortment, and reproductively isolated classes of phenotypes are a likely result of evolution only for intermediate or strong competition and for very strong assortment. The likelihood of divergence depends relatively weakly on the costs as long as they are not high. With high costs, however, increasingly strong assortment rapidly depletes all genetic variation, and strong competitive divergence is prevented.

Evolution, Molecular↗
PubMed1987

Pleomorphic adenoma with a predominantly myoepithelial proliferation of the vagina.

A case of pleomorphic adenoma of the vagina in a 44-year-old woman was described. The tumor was a submucosal mass measuring 3.5 X 2 X 2 cm and located in the left lateral wall 1.5 cm inside the introitus. Histologically, it was predominantly composed of sheets and strands of spindle-shaped or polygonal cells focally dispersed in the myxoid tissue to form pseudomicrocysts. Ultrastructure demonstrated the basal lamina, desmosomes, variable amounts of filaments of both intermediate and microfilament, and occasionally microvilli in these tumor cells indicating that dominant cells were myoepithelial in nature. With immunohistochemical studies, keratin and cytokeratin were positive, whereas, S-100 protein, glial fibrillary acidic protein, vimentin, secretory component, and lysozyme were negative. The previously published cases were reviewed and compared with the present case.

Adult↗
PubMed1988

Fluctuations in spontaneous discharge of hippocampal theta cells during sleep-waking states and PCPA-induced insomnia.

1. The spontaneous activity of hippocampal theta cells in head-restrained cats was recorded during slow-wave sleep (SWS), paradoxical sleep (PS), and the attentive state of bird watching (BW). We also recorded theta cell activity during a state of insomnia with pontogeniculoocipital (PGO) waves, which was induced by the administration of p-chlorophenylalanine (PCPA), a selective inhibitor of serotonin synthesis. 2. The time-dependent structure of fluctuations in theta cell activity was evaluated by power spectral analysis and Markovian analysis. The coefficient of variation for these time series was used as a measure of the variability of theta cell activity, which indicates the relative amplitude of fluctuations. 3. During SWS, theta cell activity showed a larger variability and a flat spectrum, i.e., low Markovian properties. During PS, this activity exhibited smaller variability and high spectral density in a low-frequency band (0.01-1.0 Hz), i.e., high Markovian properties. During BW, variability, spectral and Markovian properties were intermediate. 4. The firing pattern of theta cells during PCPA-induced insomnia was similar to that during PS. However, after the administration of either a serotonin agonist, 5-Methoxy-N,N-dimethyltryptamine, or a choline antagonist, atropine sulfate, theta cell activity no longer exhibited PS-like fluctuations, revealing instead a firing pattern similar to that during SWS. 5. During PS and PCPA-induced insomnia, not only the unit activity of theta cells, but PGO activity and theta wave frequency exhibited slow fluctuations, i.e., the high spectral density in the low-frequency band (0.01-1.0 Hz). 6. Cross-correlation analyses were performed between the fluctuations in theta cell activity, theta wave frequency, and PGO activity. These fluctuations correlated with each other during both PS and PCPA-induced insomnia. Bursts of PGO waves especially contributed to these cross-correlations. 7. These results suggest, first, that the slow fluctuations of the theta cell activity during PS and PCPA-induced insomnia is the physiological expression of the removal of aminergic influences and, secondly, that they are dependent on cholinergic mechanisms, including PGO generators.

Action Potentials↗
PubMed1993

Output organization of intermediate cerebellum of the monkey.

1. The goal of this study was to investigate the motor organization of monkey nucleus interpositus (NI) and neighboring regions of the lateral nucleus (NL) by correlating discharge of single neurons with active movements. Neurons were surveyed during free-form movements as well as during operation of six devices that required movement about specific forelimb joints. The paradigm allowed us to test the hypothesis that discharge of individual cells relates to movements about individual joints. 2. One hundred sixty-two isolated nuclear neurons from two monkeys were studied. Eighty-three percent showed large increases in discharge (an average of 3 times resting rate for forelimb neurons) during movement of one body part, either forelimb, hindlimb, mouth/face, or eyes. 3. Anterior interpositus contains neurons related to hindlimb movement in anterior regions and neurons related to forelimb movement in posterior regions. A mouth/face-related area exists in the dorsal-posterior regions and is continuous with a mouth/face area in the dorsal regions of NL. Posterior interpositus (NIP) showed no clear separation between forelimb and hindlimb neurons: forelimb neurons were encountered throughout the nucleus, and hindlimb neurons were encountered in the medial-anterior two thirds. A distinct eye movement area exists in lateral, posterior, and ventral regions of NIP. This area borders regions of NL that also contain eye movement-related neurons. 4. Forelimb interpositus neurons discharged strongly during reach and grasp; discharge rates were recorded for 41 neurons during a stereotyped reach and the average depth of modulation was 149 imp/s. Nineteen neurons that modulated during device tracking were also tested during reaching, and the depth of modulation was much greater during reaching. 5. Fifty-nine forelimb neurons were tested with device tracking. Twenty-seven (46%) produced no audible modulation, regardless of the joint being exercised. The remaining 32 neurons modulated during movement on at least one device (mean depth of modulation = 84 imp/s). Comparison of discharge during use of different devices revealed no strong evidence for device-specific discharge. 6. Discharge modulations during device tracking were phasic, preceded movement, and, for a small number of cells, showed consistent parametric relations to duration, amplitude, and velocity of movement. 7. Despite a clear somatotopy within NI and NL, there is no finer mapping based on active movements about individual joints within forelimb regions. Discharge modulation depends on movements involving the whole limb. Progress in understanding the function of intermediate cerebellum depends on determining the variables required to elicit consistent and high modulation of neural discharge.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

Hyperinsulinemia, risk factors, and coronary heart disease. The Zutphen Elderly Study.

We investigated the association between fasting insulin concentration--an indicator of insulin resistance in nondiabetic individuals--cardiovascular risk factors, and coronary heart disease in a study of 390 men in the town of Zutphen. In 1990, an extensive examination was carried out on the participating men (aged 70 to 89 years). Fasting insulin levels were determined and a number of other risk factors measured. Known and newly diagnosed diabetics were excluded from the data analyses. Fasting insulin concentration was significantly associated with levels of glucose, triglycerides, uric acid, serum albumin, creatinine, and fibrinogen as well as resting heart rate. Inverse associations with high-density lipoprotein cholesterol and factor VII activity were observed. These results were independent of confounding factors such as age, body mass index, ratio of subscapular to triceps skinfold thicknesses, cigarette smoking, physical activity, and alcohol consumption. Men with a fasting insulin level higher than 80 pmol/L (highest quartile of the distribution) had a significantly higher prevalence of coronary heart disease and especially of myocardial infarction. This result was independent of potential confounding variables as well as of possible intermediates (total and high-density lipoprotein cholesterol, hypertension, serum triglycerides, fasting glucose, and other risk factors related to fasting insulin) (odds ratio, 2.2; 95% confidence interval, 1.2-4.0). No association between fasting insulin level and hypertension or blood pressure was observed. These results show that fasting insulin is an important indicator of coronary heart disease in elderly men. Clotting factors, resting heart rate, uric acid, serum albumin, and creatinine may also play a role in this metabolic syndrome.

Aged↗
PubMedDate not supplied

Heart size in inbred strains of rats. Part 1. Genetic determination of the development of cardiovascular enlargement in rats.

The heart and aorta weights in 23 strains of rats and the four-way cross generation among the M520/N, SHRSP/N, SHR/N, and WKY/N strains were investigated in relation to their blood pressure in an attempt to characterize cardiovascular enlargement (increased weight of heart and aorta) from a genetic aspect. The distribution of blood pressure in these strains at 10 weeks of age was clearly divided into hypertensive and normotensive groups. In the hypertensive group, heart weight increased in proportion to blood pressure. In contrast, there was no relationship between blood pressure and heart weight in the normotensive group in spite of large strain differences in heart weights. The result of variance analysis exhibited a significant strain difference in heart weight, and the degree of genetic determination was estimated to be 65%-75%. A similar genetic influence was apparent for normotensive strains excluding hypertensive strains. The distribution of blood pressures in the four-way cross generation showed the segregation of three phenotypes consisting of normotensive, intermediate and hypertensive groups. A large variability was seen in heart weight of each group. However, the increase in average heart weight of these three groups was very small. The degree of genetic determination from the cross analysis was estimated to be 45%-65%. These results indicate that heart weight is a highly heritable trait, and that the effect of genetic factors on cardiac enlargement is larger than that of blood pressure. A similar result was obtained for the aorta weight. However, the effect of genetic factors was less important for aorta weight than for heart weight since the degree of genetic determination was estimated to be 45%-65% from the strain comparison and 35%-60% from the cross analysis.

Age Factors↗